pubmed > ABL1 > cytogenetic

Overview of clinical and genetic features of CML patients with variant Philadelphia translocations involving chromosome 7: A case series.
Variant Philadelphia (Ph) translocations involving chromosome 7 are rarely seen in Chronic Myeloid Leukemia (CML) patients. It is aimed to contribute new cases to the literature by reviewing the cases in our archive and shed light into the understanding of the role of chromosome 7 in CML. This study was carried out in 237 newly diagnosed CML patients with variant Ph translocations. Among the patients, those with variant Ph translocation involving chromosome 7 were evaluated in terms of clinical and genetic characteristics. Chromosome analysis was performed on 24 and 48 h of bone marrow cultures. FISH analysis was performed with BCR-ABL1 dual color dual fusion translocation probes. BCR-ABL1 transcript levels were analysed by QRT-PCR and results were reported as BCR-ABL1/ABL1 (BCR-ABL1 (IS) %) according to international scale. Four of the patients had variant Ph translocations including chromosome 7. The karyotypes were 46,XX,t(7;9;22)(p13;q34;q11); 46,XX,t(7;9;22)(p21;q34;q11); 46,XX,t(7;9;22)(q22;q34;q11) and 46,XY,t(7;9;22)(q22;q34;q11). The breakpoints demonstrated by cytogenetic analysis were confirmed by FISH analysis. Monitoring by QRT-PCR showed that patients with variant Ph translocation including 7p13 and 7p21 had a dramatic decrease in BCR-ABL1 levels resulting in complete hematological, complete cytogenetic and deep molecular responses. Despite achieving complete hematological, complete cytogenetic response in two patients with variant Philadelphia translocation, including 7q22, no major molecular response was achieved and both patients are still in the warning category. Response to tyrosine kinase inhibitör therapy may be associated with both the variant translocation mechanism and new gene interactions that occur due to the breakpoints of additional chromosomes involved in translocation.
Publication Date: 2021-10-12
Journal: Leukemia research

H396P mutation in chronic myeloid leukaemia patient on nilotinib - A case report.
The advent of BCR-ABL1-targeted therapy with the tyrosine kinase inhibitor (TKI), for example, imatinib and nilotinib, marked a turning point in the therapy of chronic myeloid leukaemia (CML). However, a substantial proportion of patients experience primary or secondary disease resistance to TKI. There are multifactorial causes contributing to the treatment failure of which BCR-ABL1 kinase domain mutation being the most common. Here, we describe a case of a CML patient with H396P mutation following treatment with nilotinib. A 60-year-old woman presented with abdominal discomfort and hyperleukocytosis. She was diagnosed as CML in the chronic phase with positive BCR-ABL1 transcripts. Due to the failure to obtain an optimal response with imatinib treatment, it was switched to nilotinib. She responded well to nilotinib initially and achieved complete haematological and cytogenetic responses, with undetectable BCR-ABL1 transcripts. However, in 4 years she developed molecular relapse. Mutation analysis which was done 70 months after commencement of nilotinib showed the presence of BCRABL1 kinase domain mutation with nucleotide substitution at position 1187 from Histidine(H) to Proline(P) (H396P). Currently, she is on nilotinib 400mg twice daily. Her latest molecular analysis showed the presence of residual BCR-ABL1 transcripts at 0.22%. This case illustrates the importance of BCR-ABL1 mutation analysis in CML patients with persistent BCR-ABL1 positivity in spite of treatment. Early detection and identification of the type of BCRABL1 mutation are important to guide appropriate treatment options as different mutation will have different sensitivity to TKI.
Publication Date: 2021-04-28
Journal: The Malaysian journal of pathology

BCR/ABL1 fluorescence
The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation.
Publication Date: 2021-04-08
Journal: Hematology reports

An Idic(7)(q11.2) Resulting in Two Copies of 7p and Deletion 7q: A Rare Cytogenetic Event in a Case of Acute Myeloid Leukemia.
A 67-year-old male patient was diagnosed with acute myeloid leukemia (AML) in April 2018. Chromosome analysis showed an abnormal male karyotype with an isodicentric chromosome 7q resulting in deletion 7q and two copies of 7p and a derivative chromosome 18 in 13 of the 20 metaphase cells examined. This karyotype was described as 46,XY,idic(7)(q11.2),der(18)t(1;18)(q23;q21.1)[13]/46,XY[7]. Additionally, subsequent sequencing analysis displayed FLT3-ITD and RUNX1 mutations (data not shown). The bone marrow showed an overwhelming number of blast cells, with co-expression of CD34, CD117, TdT, MPO, CD7, CD13, CD33, CD38, CD19, and HLA-DR. Molecular cytogenetic studies showed a deletion of one RELN/TES (7q22/7q31) signal in 80.5% of nuclei and a gain of a BCR/ABL1 (22q11.2/9q34) signal in 3.5% of interphase nuclei examined. These findings were described as nuc ish(RELN,TES)x1[161/200],(ABL1x2,BCRx3)[7/200], (EVI1,TAS2R1,EGR1,DEK,MYC,NUP214,KMT2A,DLEU1,DLEU2,Clone 163C9,PML,CBFB,RARA,PTPRT,MYBL2,RUNX1)x2[200]. The patient relapsed with AML in September 2019 and underwent treatment. However, all AML treatment options were exhausted by March 2020. An isodicentric chromosome 7 leading to two copies of the short arm of chromosome 7 (7p) and deletion 7q is a rare event in AML and is rarely described in the literature. The key element here is that this specific rearrangement leads to deletion 7q which is a well-known abnormality in AML that places the patient in the Poor/Adverse risk category.
Publication Date: 2021-03-09
Journal: Journal of the Association of Genetic Technologists

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center.
Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p=0.010) disease with frequent ETV6-RUNX1 fusion (p=0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p=0.001), especially for the frequent presence of BCR-ABL1 fusion (p=0.004) and KMT2A rearrangement (p=0.045). CD7-expressing B-ALL patients had inferior event-free survival (p=0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p=0.317). In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.
Publication Date: 2021-02-03
Journal: Hematology, transfusion and cell therapy

A multicenter retrospective evaluation of Chronic Myeloid Leukemia (CML) therapy in Austria assessing the impact of early treatment response on patient outcomes in a real-life setting : R-EFECT study.
Several clinical trials in chronic phase (CP) chronic myeloid leukemia (CML) showed that early response to tyrosine kinase inhibitor (TKI) treatment results in an improved long-term survival and progression-free survival. This study assessed whether patients achieving early treatment response (ETR; partial cytogenetic response or BCR-ABL1 mRNA ≤10% at 3 months) in daily practice also have a long-term survival benefit. The Retrospective Evaluation of Early response in CML for long-term Treatment outcome (R-EFECT), a multicenter, retrospective chart review, documented patients with newly diagnosed CML-CP starting first-line TKI therapy in routine clinical practice. The primary aim was to assess the 5‑year overall survival rate. Of the 211 patients from 12 centers across Austria (January 2004-May 2010), 176 (median age, 56 years) were included in the analysis. All patients received first-line therapy with imatinib. Overall, 136 patients (77.3%) achieved ETR (ETR+ group), whereas 40 (22.7%) did not reach ETR (ETR- group). The ETR+ group had higher 5‑year overall survival (92.5% vs. 77.5%, P = 0.018) and progression-free survival (95.6% vs. 87.5%, P = 0.06) rates compared with the ETR- group. As expected, more patients in the ETR- group were switched to another TKI. At the last contact, 120 patients were still on imatinib and 44 had switched to another TKI (25 to nilotinib, 15 to dasatinib, and 4 to bosutinib). The data are in line with randomized trials demonstrating that ETR is associated with improved survival and thus confirmed these results in patients treated in daily clinical routine.
Publication Date: 2020-06-14
Journal: Wiener klinische Wochenschrift

A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review.
BACKGROUND Single or multiple cell line dysplasia is a characteristic feature of myelodysplastic syndrome. However, significant dysgranulopoiesis is not a feature of chronic myeloid leukemia (CML). Systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN) comprises 5% to 40% of cases of SM. All types of hematologic neoplasms have been previously reported, although CML has been rarely encountered. CASE REPORT A 28-year-old male presented with a 3-month-history of weight loss and massive splenomegaly. Peripheral blood revealed marked leukocytosis, shift to left with 13% blasts. There was evident dysgranulopoiesis that raised a provisional diagnosis of myelodysplastic/myeloproliferative neoplasm. Bone marrow (BM) examination revealed granulocytic hyperplasia with 10% blasts and significant dysgranulopoiesis. Unexpectedly, cytogenetic analysis revealed t(9;22) with BCR/ABL1 rearrangement, diagnostic of chronic myeloid leukemia in an accelerated phase. The patient was started on dasatinib 100 mg upfront, however, he failed to respond, with increasing leukocytosis. Repeat BM examination showed persistence of the findings with 8% blasts. At this time, aggregates of mast cells with aberrant expression of CD25 were elicited, thus concluding the diagnosis of SM-AHN. The patient failed multiple lines of treatment (dasatinib, nilotinib, hydroxyurea, cytarabine subcutaneous, 6-mercaptopurine and interferon) and progressed to the blast phase a few months later. CONCLUSIONS We report an unusual case of CML, presented with significant dysgranulopoiesis with an aggressive clinical course including SM uncovered during the disease course with subsequent transformation to the blast phase. The different biological behavior of this case underscores the need for studies on a larger number of cases to explore the significance of the aforementioned coexistent features.
Publication Date: 2020-05-14
Journal: The American journal of case reports

[18F-fluorodeoxyglucose-positron emission tomography imaging before and after treatment of chronic-phase chronic myeloid leukemia with tyrosine kinase inhibitors].
A 64-year-old man presented with abnormal imaging results on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing moderately increased FDG-uptake in the entire bone marrow. Blood tests revealed leukocytosis, thrombocytosis, and increased lactate dehydrogenase levels. Furthermore, the neutrophil alkaline phosphatase score decreased. Bone marrow examination revealed marked hypercellularity of myeloid and megakaryocytic lineages without an excess of blasts. Cytogenetic analysis of the bone marrow demonstrated Philadelphia chromosome, and fluorescence in situ hybridization analysis was positive for BCR-ABL1 fusion genes. Thus, the patient was diagnosed with chronic myeloid leukemia (CML) in the chronic phase and tyrosine kinase inhibitor therapy with 100 mg of dasatinib daily was initiated. Complete cytogenetic response and a major molecular response were achieved at 3 and 12 months post-treatment, respectively. FDG-uptake values of the bone marrow remarkably decreased along with the remission status of the disease. FDG-PET images at pre- and post-treatment of CML are rarely compared, so we report this case as an important reference.
Publication Date: 2020-05-08
Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology

Long-term results of frontline dasatinib in chronic myeloid leukemia.
Dasatinib is a second-generation tyrosine kinase inhibitor that, when used as frontline therapy, produces more and faster cytogenetic and molecular responses compared with imatinib. The authors report the long-term follow-up from the first study using dasatinib as initial therapy for chronic-phase chronic myeloid leukemia. Between November 2005 and August 2014, patients were randomly assigned to receive 100 mg daily or 50 mg twice daily. After June 2009, all patients started with 100 mg daily. With a median follow-up of 6.5 years, 94 of 149 treated patients (63%) were still receiving dasatinib on study. The median patient age was 48 years (interquartile range, 37-55 years), and 9% of patients had a high risk Sokal risk score. The cumulative complete cytogenetic response rate at 11 years was 92.6%, the major molecular response (MR) rate was 88.2%, and the MR4.5 rate (indicating a ≥4.5-log reduction in BCR-ABL1 transcripts) was 79.5%. The median time to a major MR and MR4.5 was 6 and 23 months, respectively. A sustained MR4.5 (≥2 years) was achieved in 82 patients (55%). The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival. The most common reasons for treatment discontinuation were toxicity and elective discontinuation. The most common treatment-emergent grade 3 and 4 adverse events were fatigue, thrombocytopenia, and infections. After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses and MRs, durable deep MRs, and excellent long-term survival outcomes in patients with chronic-phase chronic myeloid leukemia.
Publication Date: 2020-01-31
Journal: Cancer

Clinical implications of cytogenetic heterogeneity in Philadelphia chromosome positive (Ph+) adult B cell acute lymphoblastic leukemia following tyrosine kinase inhibitors and chemotherapy regimens.
We retrospectively studied a cohort of 144 adults with Philadelphia chromosome/BCR-ABL1 positive B acute lymphoblastic leukemia (Ph + B-ALL) to assess the clinical implications of cytogenetic heterogeneity in this disease. The study group included 85 men and 59 women that were sorted into 6 subgroups based on karyotypic findings in the stemline as follows: 32 patients with t(9;22) as a sole aberration, 23 with t(9;22) plus 1 additional chromosomal abnormality (ACA), 26 with t(9;22) as part of a complex karyotype, 18 showing a variant-/complex- t(9;22), 30 with t(9;22) as the stemline with ACAs in the sideline(s), and 15 patients who had the t(9;22) and hyperdiploidy. In 89 patients 1 clone was identified; 41 had 2 clones and 14 had ≥ 3 clone(s). The median overall survival (OS) was 25.6 months and the median relapse-free survival (RFS) was 20.6 months. Patients with variant-/complex- t(9;22) had poorer OS and RFS when compared with all other subgroups combined (P = 0.0018 and P = 0.0049, respectively). In addition, patients with ≥ 2 clones had worse OS and RFS than patients with 1 clone (P = 0.0179 and P = 0.0429, respectively). Multivariate analysis confirmed that variant-/complex-t(9;22) and clone number are independent risk factors. We suggest that conventional chromosomal analysis is of clinical importance for risk stratification of B-ALL patients.
Publication Date: 2019-07-07
Journal: Leukemia research

Efficacy of Dasatinib in a Very Elderly CML Patient Expressing a Rare E13a3
We report the case of an 89-year-old male diagnosed with chronic-phase CML and expressing a rare e13a3 BCR-ABL1 fusion transcript. His cytogenetic analysis showed the t(9;22) translocation generating the Philadelphia chromosome (Ph), with a multiplex RT-PCR detecting an atypical fragment. Using two primers complementary to exon 10 of BCR and exon 4 of ABL1, a larger PCR product was observed, where after Sanger sequencing, an e13a3 BCR-ABL1 transcript was revealed. Given the diagnosis, the patient received 100 mg of dasatinib every other day and was then monitored by measuring both hematological and cytogenetic parameters, while his BCR-ABL1 transcripts were examined by PCR and semi-nested-PCR. According to the 2013 European Leukemia Network criteria, after six months of dasatinib the patient's response was classified as warning as he displayed 20% of Philadelphia-positive metaphases. Sequencing of the ABL1 catalytic domain did not detect point mutations. A complete cytogenetic response was achieved after one year of dasatinib. However, semi-nested-PCR confirmed the presence of the e13a3 BCR-ABL1 fusion transcript that has persisted up to the latest follow-up visit.
Publication Date: 2019-07-03
Journal: Anticancer research

Clinical characteristics and prognostic significance of chronic myeloid leukemia with rare BCR-ABL1 transcripts.
The prognostic significance of rare BCR-ABL1 transcripts is uncertain in the tyrosine kinase inhibitor (TKI) era. In this retrospective study, 40 (1.7%) patients with rare BCR-ABL1 transcripts were identified from a cohort of 2331 chronic myeloid leukemia (CML) patients; 4 types of rare transcripts were identified, including e1a2 (0.9%), e19a2 (0.4%), e13a3 (0.1%), and e14a3 (0.3%). Compared to patients with the typical transcript, those with the e1a2 transcript had an inferior response to TKIs and a worse outcome. Patients with the e19a2 transcript had a high rate of early optimal response to TKIs, but most of them later lost the complete cytogenetic response (CCyR) due to BCR-ABL1 mutations, resulting in a poor prognosis. Patients with the e13a3/e14a3 transcript responded well to TKIs and had a good outcome. These findings indicate that the type of BCR-ABL1 transcript should be considered when determining the treatment for CML patients in the TKI era.
Publication Date: 2019-07-02
Journal: Leukemia & lymphoma

Ten-year outcome of chronic-phase chronic myeloid leukemia patients treated with imatinib in real life.
Imatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2 years (range 5.8-14.8), the long-term outcome, efficacy, and safety of imatinib treatment (frontline and after interferon failure) in a single institution cohort of 459 patients with CML in chronic phase treated outside of clinical trials. The 10-year overall survival of the whole cohort was 77.1%, while the 10-year probability of dying due to CML and other causes was 7.8% and 16%, respectively. The prognostic value of the BCR-ABL1 ratio at 3 months (⩽ 10%) and of complete cytogenetic response and major molecular response at 1 year was confirmed also in the real-life practice. The EUTOS long-term survival score better stratified the baseline risk of dying of CML compared with other risk scores. Two hundred thirty-six (51.4%) patients achieved a deep molecular response during imatinib treatment after a median time of 4.57 years, and 95 (20.6%) had a stable deep molecular response maintained for at least 2 consecutive years. Imatinib was associated with a low rate of serious cardiovascular events and second neoplasia. This 10-year real-life follow-up study shows that imatinib maintains efficacy over time and that long-term administration of imatinib is not associated with notable cumulative or late toxic effects.
Publication Date: 2019-05-13
Journal: Annals of hematology

Primary Cutaneous T-Cell Lymphoblastic Lymphoma: Case Report and Literature Review.
Cutaneous involvement by precursor T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is rare, and almost all cases are seen in association with bone marrow, blood, and/or lymph node involvement. Presentation with isolated skin involvement is very rare. Literature review revealed only one case report of primary cutaneous T-cell LBL. We discuss here another patient diagnosed with primary cutaneous T-cell LBL at our institute. This patient was initially misdiagnosed as having peripheral T-cell lymphoma NOS. Cytogenetic analysis showed the CDKN2A deletion (-9p21×2) in addition to three intact copies of ABL1 (+9q34). Although she failed multiple lines of intensive chemotherapy, her disease remained confined to the skin. We believe that this presentation of T-LBL is underreported, and many patients are likely misdiagnosed as having high-grade cutaneous T-cell lymphomas. With this case and literature review, we would like to highlight the importance of keeping lymphoblastic lymphoma on the differential diagnosis of cutaneous T-cell lymphoma-like lesions to avoid delay in diagnosis and inappropriate treatment of this aggressive disease.
Publication Date: 2019-03-28
Journal: Case reports in hematology

Flow cytometric predictive scoring systems for common fusions ETV6/RUNX1, BCR/ABL1, TCF3/PBX1 and rearrangements of the KMT2A gene, proposed for the initial cytogenetic approach in cases of B-acute lymphoblastic leukemia.
In B-acute lymphoblastic leukemia (B-ALL), the identification of cytogenetic prognostic factors is important for stratifying patients into risk groups and tailoring treatment accordingly. The purpose of this study was to propose flow cytometric (FCM) scoring systems (SSs) for predicting t(12;21)(p13;q22), t(9;22)(q34;q11), t(11q23), and t(1;19)(q23;p13.3) translocations. We analyzed retrospectively the FCM immunophenotype of 377 patients with B-ALL with regard to the major cytogenetic findings revealed by interphase fluorescence in situ hybridization (i-FISH). Comparing descriptive data on the expression of each antigen and performing receiver operating characteristic (ROC) analysis, we identified the most reliable predictive markers for each translocation and sought to establish a specific SS for each translocation, based on specific antibody panels. CD27, CD9, CD66c, CD10, CD25, and CD34 were employed for the prediction of t(12;21), CD25, CD38, CD34, and CD66c for t(9;22), NG2, CD10, CD15, CD34, and CD20 for t(11q23), and CD34, cμ, CD123, and CD66c for t(1;19). The sensitivity and specificity, respectively, of each predictive score were 89.29% and 96.15% for t(12;21), 75.00% and 88.19% for t(9;22), 84.21% and 99.04% for t(11q23), and 85.71% and 92.71% for t(1;19). Four highly specific and significantly sensitive FCM-obtained SSs are proposed for the prediction of the four major translocations observed in patients with B-ALL. Prospective evaluation of the proposed SSs could lead to a better targeted cytogenetic investigation and therefore to more cost-effective laboratory practice.
Publication Date: 2019-02-08
Journal: International journal of laboratory hematology

A Case of Chronic Myelogenous Leukemia Occurring in a Patient Treated for Essential Thrombocythemia.
BACKGROUND Essential thrombocythemia (ET) is one of the BCR-ABL gene fusion negative chronic myeloproliferative disorders (MPDs), which also include polycythemia vera (PV), and myelofibrosis. Few clinical cases have reported the progression of ET to chronic myelogenous leukemia (CML) with the expression of the BCR-ABL gene. This report describes such a case and includes a review of other reported cases of CML co-occurring with BCR-ABL-negative chronic MPDs. CASE REPORT A 49-year-old woman was diagnosed with ET in 2007. Cytogenetic testing was negative for expression of the JAK2 or BCR-ABL1 genes. Eight years later, in January 2015, she presented with excessive fatigue, poor appetite, unintentional weight loss, a white blood cell (WBC) count of 24,700 per mL, hemoglobin of 9.9 g/dl, and a platelet count of 557,000 per mL, with blasts and basophils in the blood film. Cytogenetic analysis with fluorescent in situ hybridization (FISH) confirmed a 9: 22 chromosomal translocation (Philadelphia chromosome), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression of the BCR-ABL gene, confirming a diagnosis of CML. In February 2015, first-line therapy commenced with nilotinib, which was changed to imatinib after three months. During the following nine months, qRT-PCR confirmed a trend to deep molecular remission (MR5). However, she developed early myelofibrosis, and myelosuppressive therapy was resumed. CONCLUSIONS This rare case highlights the importance of cytogenetic testing in cases of CMPD that transform to CML, not only to confirm the diagnosis but to plan treatment, as Philadelphia chromosome-positive and -negative cases differ in their management.
Publication Date: 2019-01-04
Journal: The American journal of case reports

Keeping PACE with Ph Positive to Ph-Like Detection in B-Lineage Acute Lymphoblastic Leukemia: A Practical and Cost Effective (PACE) Approach in a Resource Constrained Setting.
Philadelphia (Ph)-like or BCR-ABL like acute lymphoblastic leukemia (ALL) is defined on the basis of a gene expression profile that is similar to Ph-positive ALL. It comprises a wide spectrum of genetic lesions affecting primarily the cytokine receptor and/or kinase signalling genes. It accounts for approximately 10-15% of pediatric ALL, and is more common in patients who are high-risk according to the National Cancer Institute criteria. Presence of Ph-like mutations is an independent predictor of poor outcome. However, there is vast potential to utilize targeted therapy to improve survival in this group. The sizeable range of genetic lesions varying from translocations, fusions, point mutations and deletions make the diagnosis challenging. Hence, a practical and cost effective approach is required to enable identification in resource constrained settings. Patients with recurrent cytogenetic abnormalities such as ETV6-RUNX1, high hyperdiploidy, TCF3-PBX1, BCR-ABL1 and KMT2A (MLL) rearrangement need not be tested, as these are mutually exclusive with BCR-ABL like mutations. Detection of CRLF2 overexpression, which is the commonest abnormality, is employed as the first step. In patients lacking overexpression, testing for tyrosine kinase fusions can be performed. However, the goal should be to employ a combination of molecular diagnostic techniques such as reverse transcriptase polymerase chain reaction (PCR), real time quantitative PCR, fluorescence in situ hybridization and Sanger sequencing to detect genetic lesions that are amenable to targeted therapy.
Publication Date: 2018-10-30
Journal: Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion

Outcomes of 219 chronic myeloid leukaemia patients with additional chromosomal abnormalities and/or tyrosine kinase domain mutations.
To confirm the role of additional chromosomal abnormalities (ACAs) and kinase domain (KD) mutations in the progression and outcomes of Chronic myeloid leukaemia (CML) patients and the connection between them, we analysed the ACAs and KD mutations of 219 CML patients admitted to our hospital. Cytogenetic analysis of metaphases was performed to detect ACAs, and the BCR-ABL1 KD was sequenced to detect KD mutations. Twenty-four patients (11.0%) had ACAs in addition to the BCR-ABL1 or t(9;22)(q34;q11) translocation. The most common abnormality was trisomy 8. Twelve different KD mutations were observed in 13 out of 53 imatinib-resistant patients (24.5%). p.(Y235H) (n = 3; 23.07%), p.(F359V) and p.(T315I) (n = 2; 15.38%) presented most frequently. KD mutations subtypes (p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V)) coexisted with ACAs. The incidence of CML progression was 12/22 (54.5%) in the group of patients with ACAs and/or KD mutations and 2/143 (1.4%) in the group of patients without ACAs or KD mutations (CI 95%, P < 0.001) and was higher in the KD mutations group than in the ACAs group (P = 0.046). The group of patients with ACAs and/or KD mutations had more men than the group of patients without ACAs or KD mutations (P = 0.013). We conclude that ACAs and/or KD mutations are related to CML progression and are adverse outcome factors. Their presence exhibits gender differences and is more common in males. p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V) emerge more frequently when ACAs and KD mutations coexist.
Publication Date: 2018-10-05
Journal: International journal of laboratory hematology

Risk of subsequent myeloid neoplasms after radiotherapy treatment for a solid cancer among adults in the United States, 2000-2014.
Although increased risk of acute myeloid leukemia (AML) has been observed after chemotherapy and radiotherapy, less is known about radiotherapy-related risks of specific AML subtypes and other specific myeloid neoplasms. We used the US population-based cancer registry data to evaluate risk of myeloid neoplasms among three cohorts of cancer survivors initially treated with radiotherapy only. We included 1-year survivors of first primary thyroid (radioiodine only, stages I-IV; N = 49 879), prostate (excluding stage IV; N = 237 439), or uterine corpus cancers (stage I-II; N = 16 208) diagnosed during 2000-2013. We calculated standardized incidence ratios (SIRs) and excess absolute risks (EARs). Thyroid cancer survivors had significantly elevated risks of total AML (SIR = 2.77, 95% CI: 1.99-3.76), AML with cytogenetic abnormalities (SIR = 3.90, 95% CI: 1.57-8.04), AML with myelodysplasia-related changes (SIR = 2.87, 95% CI: 1.05-6.25), and BCR-ABL1-positive chronic myelogenous leukemia (CML) (SIR = 5.38, 95% CI: 2.58-9.89). Irradiated prostate and uterine corpus cancer survivors were at elevated risk for total AML (SIR = 1.14, 95% CI: 1.03-1.27 and SIR = 1.77, 95% CI: 1.01-2.87, respectively), AML with cytogenetic abnormalities (SIR = 2.52, 95% CI: 1.84-3.37 and SIR = 7.21, 95% CI: 2.34-16.83, respectively), and acute promyelocytic leukemia (SIR = 3.20, 95% CI: 2.20-4.49 and SIR = 8.88, 95% CI: 2.42-22.73, respectively). In addition, prostate cancer survivors were at increased risk of BCR-ABL1-positive CML (SIR = 2.11, 95% CI: 1.52-2.85). Our findings support the importance of diagnostic precision in myeloid neoplasm classification since susceptibility following radiotherapy may vary by myeloid neoplasm subtype, thereby informing risk/benefit discussions in first primary cancer treatment.
Publication Date: 2018-05-26
Journal: Leukemia

Priapism as the initial sign in hematologic disease: Case report and literature review.
Priapism is an uncommon sign and sometimes considered a diagnosis challenge into systemic disease; this is defined as ≥4 h continuous penile erection, without sexual stimulation. We state that this work has been reported in line with the SCARE criteria PRESENTATION OF CASE: A Mexican 52-year-old man was brought to the emergency room with priapism of six days of evolution. His medical history reported fatigue and waxy pallor had begun a month ago, the rest of interrogation was unremarked. Hyperleukocitosis (>250,000 cells/ml) was documented on his preoperative evaluation, the initial step was hematology consultation due to malignance suspicion, followed by corpora cavernosa drainage-irrigation and surgery penis shunts. After of procedure, we realized bone marrow aspiration, kariotype and cytogenetic analysis, histopathological and moleculars assay reported myeloid hyperplasia compatible with acute phase CML and Philadelphia translocation t(9:22) (q34;q11.2) with P210 BCR-ABL1 fusion transcriber, patient was discharged with dasatinib for maintenance phase. Actually, he has a satisfactory evolution without relapses. The majority of reported cases shows the individual importance of hematological diseases in priapism as it is shown in the analysis of the literature of 10 years (2006-2016) that we made. It is imperative to consider the type of priapism, and the genetic and demographic patient aspects due to the early and correct approach improves the short and long term outcome of the hematological patients. Priapism is an uncommon sign of systemic disease. In the presence of warning signs, malignancy should be considered until proven otherwise.
Publication Date: 2018-02-08
Journal: International journal of surgery case reports

chronic myeloid leukemia patients(11)

bcr-abl1 tyrosine kinase(10)

acute myeloid leukemia(9)

kinase domain mutations(8)

bcr-abl1 transcript level(8)

breakpoint cluster region(8)

bcr-abl1 fusion transcript(7)

hybridization fish(10)

q34 q11(7)

≤ 10(7)

leukaemia cml(7)

inhibitors tkis(7)

response ccyr(6)

phase cml-cp(6)

ph chromosome(5)

response mmr(5)

leukemia b-all(5)

reaction rt-pcr(5)

leukemia aml(5)

pdgfra pdgfrb(4)

der 22(3)

international standard(3)