pubmed > ABL1 > inhibitors tkis

The cure of leukemia through the optimist's prism.
Progress is occurring at a dizzying rate across all leukemias. Since the authors' review of the topic in Cancer in 2018, numerous discoveries have been made that have improved the therapy and outcomes of several leukemia subsets. Hairy cell leukemia is potentially curable with a single course of cladribine followed by rituximab (10-year survival, ≥90%). Acute promyelocytic leukemia is curable at a rate of 80% to 90% with a nonchemotherapy regimen of all-trans retinoic acid and arsenic trioxide. The cure rate for core-binding factor acute myeloid leukemia (AML) is ≥75% with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin. Survival for patients with chronic myeloid leukemia is close to that for an age-matched normal population with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Chronic lymphocytic leukemia, a previously incurable disease, may now be potentially curable with a finite duration of therapy with Bruton tyrosine kinase inhibitors and venetoclax. The estimated 5-year survival rate for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) exceeds 70% with intensive chemotherapy and ponatinib, a third-generation BCR-ABL1 TKI, and more recent nonchemotherapy regimens using dasatinib or ponatinib with blinatumomab are producing outstanding results. Survival in both younger and older patients with ALL has improved with the addition of antibodies targeting CD20, CD19 (blinatumomab), and CD22 (inotuzumab) to chemotherapy. Several recent drug discoveries (venetoclax, FLT3 and IDH inhibitors, and oral hypomethylating agents) are also improving outcomes for younger and older patients with AML and for those with higher risk myelodysplastic syndrome.
Publication Date: 2021-10-07
Journal: Cancer

Imatinib co-loaded targeted realgar nanocrystal for synergistic therapy of chronic myeloid leukemia.
Discovery of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has revolutionized the therapy of chronic myeloid leukemia (CML), a malignant myeloproliferative disease characterized by abnormal activation of BCR-ABL fusion oncoprotein with protein tyrosine kinase (PTK) activity. However, the long-term treatment outcomes with TKIs are strongly limited by multiple drug resistances, resulting in relapse albeit with initial high response rate. Here, we reported a realgar (As
Publication Date: 2021-08-25
Journal: Journal of controlled release : official journal of the Controlled Release Society

Impact of frontline treatment approach on outcomes of myeloid blast phase CML.
The natural course of untreated chronic myeloid leukemia (CML) is progression to an aggressive blast phase. Even in the current era of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the outcomes of blast phase CML remain poor with no consensus frontline treatment approach. We retrospectively analyzed the response rates and survival outcomes of 104 consecutive patients with myeloid blast phase CML (CML-MBP) treated from 2000 to 2019 based on 4 different frontline treatment approaches: intensive chemotherapy (IC) + TKI (n = 20), hypomethylating agent (HMA) + TKI (n = 20), TKI alone (n = 56), or IC alone (n = 8). We also evaluated the impact of TKI selection and subsequent allogeneic stem cell transplant (ASCT) on patient outcomes. Response rates were similar between patients treated with IC + TKI and HMA + TKI. Compared to treatment with TKI alone, treatment with IC/HMA + TKI resulted in a higher rate of complete remission (CR) or CR with incomplete count recovery (CRi) (57.5% vs 33.9%, p < 0.05), a higher complete cytogenetic response rate (45% vs 10.7%, p < 0.001), and more patients proceeding to ASCT (32.5% vs 10.7%, p < 0.01). With a median follow-up of 6.7 years, long-term outcomes were similar between the IC + TKI and HMA + TKI groups. Combination therapy with IC/HMA + TKI was superior to therapy with TKI alone, including when analysis was limited to those treated with a 2nd/3rd-generation TKI. When using a 2nd/3rd-generation TKI, IC/HMA + TKI led to lower 5-year cumulative incidence of relapse (CIR; 44% vs 86%, p < 0.05) and superior 5-year event-free survival (EFS; 28% vs 0%, p < 0.05) and overall survival (OS; 34% vs 8%, p = 0.23) compared to TKI alone. Among patients who received IC/HMA + TKI, EFS and OS was superior for patients who received a 2nd/3rd generation TKI compared to those who received imatinib-based therapy. In a landmark analysis, 5-year OS was higher for patients who proceeded to ASCT (58% vs 22%, p = 0.12). Compared to patients treated with TKI alone for CML-MBP, treatment with IC + TKI or HMA + TKI led to improved response rates, CIR, EFS, and OS, particularly for patients who received a 2nd/3rd-generation TKI. Combination therapy with IC + TKI or HMA + TKI, rather than a TKI alone, should be considered the optimal treatment strategy for patients with CML-MBP.
Publication Date: 2021-06-17
Journal: Journal of hematology & oncology

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1
Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. By inhibiting the BCR-ABL1 kinase, crizotinib efficiently suppressed growth of Ph+ cells without affecting growth of Ph- cells. It was also active in Ph+ patient-derived long-term cultures (PD-LTCs) independently of the responsiveness/resistance to other TKIs. The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1
Publication Date: 2021-06-11
Journal: Annals of hematology

Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells.
Chronic myeloid leukemia (CML) develops due to the presence of the BCR-ABL1 protein, a target of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), used in a CML therapy. CML eradication is a challenge due to developing resistance to TKIs. BCR-ABL1 induces endogenous oxidative stress leading to genomic instability and development of TKI resistance. Model CML cells susceptible or resistant to IM, as well as wild-type, non-cancer cells without the BCR-ABL1 protein were treated with IM, hydrogen peroxide (H
Publication Date: 2021-05-01
Journal: Biomolecules

Efficacy and safety of ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case series from a single institute.
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is an aggressive leukemia that occurs in 20-40% of adult patients. Ph + ALL is caused by the Philadelphia chromosome (Ph), which consists of a t(9;22)(q34;q11) reciprocal translocation leading to the formation of a BCR-ABL1 fusion gene. The disease is treated with targeted therapy comprising ABL1 tyrosine kinase inhibitors (TKIs). Ponatinib is a third generation TKI that demonstrates higher binding affinity for ABL1 than first/second generation TKIs. Although intensive combined immunotherapy with ponatinib greatly improves the prognosis of Ph + ALL, the safety and efficacy profiles of ponatinib in Japanese patients are unclear. This retrospective study investigated five cases of Ph + ALL at a single institute to evaluate safety and efficacy profiles. Three patients achieved a deep molecular response (DMR) following combined intensive treatment with ponatinib as induction chemotherapy. Four patients received consolidative allogenic stem cell transplantation (allo-SCT) during their first complete response. Three of the four experienced early relapse within 100 days; they subsequently received ponatinib, and one of the three achieved a DMR. No patient experienced severe cardiovascular events. This case series suggests that ponatinib at a concentration of least 30 mg exhibits anti-leukemia effects in Japanese patients with Ph + ALL.
Publication Date: 2021-04-29
Journal: International journal of hematology

Predictive value of tyrosine phosphatase receptor gamma for the response to treatment tyrosine kinase inhibitors in chronic myeloid leukemia patients.
Protein tyrosine phosphatase receptor gamma (PTPRG) is a member of the receptor-like family protein tyrosine phosphatases and acts as a tumor suppressor gene in different neoplasms. Recent studies reported the down-regulation of PTPRG expression levels in Chronic Myeloid Leukemia disease (CML). In addition, the BCR-ABL1 transcript level is currently a key predictive biomarker of CML response to treatment with Tyrosine Kinase Inhibitors (TKIs). The aim of this study was to employ flow cytometry to monitor the changes in the expression level of PTPRG in the white blood cells (WBCs) of CML patients at the time of diagnosis and following treatment with TKIs. WBCs from peripheral blood of 21 CML patients were extracted at diagnosis and during follow up along with seven healthy individuals. The PTPRG expression level was determined at protein and mRNA levels by both flow cytometry with monoclonal antibody (TPγ B9-2) and RT-qPCR, and BCR-ABL1 transcript by RT-qPCR, respectively. PTPRG expression was found to be lower in the neutrophils and monocytes of CML patients at time of diagnosis compared to healthy individuals. Treatment with TKIs nilotinib and Imatinib Mesylate restored the expression of PTPRG in the WBCs of CML patients to levels observed in healthy controls. Moreover, restoration levels were greatest in optimal responders and occurred earlier with nilotinib compared to imatinib. Our results support the measurement of PTPRG expression level in the WBCs of CML patients by flow cytometry as a monitoring tool for the response to treatment with TKIs in CML patients.
Publication Date: 2021-04-25
Journal: Scientific reports

Dosing Strategies for Improving the Risk-Benefit Profile of Ponatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase.
The treatment of chronic myeloid leukemia (CML) has been advanced by the development of small-molecule tyrosine kinase inhibitors (TKIs), which target the fusion protein BCR-ABL1 expressed by the Philadelphia chromosome. Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with high affinity and inhibits most BCR-ABL1 mutants, including the T315I mutation. The approved starting dose of ponatinib is 45 mg once daily (full dose), however, the need for a full dose, especially in patients with dose adjustments due to tolerability problems, remains undemonstrated. Lower starting doses of ponatinib (30 mg or 15 mg once daily) for patients "with lesser degrees of resistance or multiple intolerances, especially those with an increased cardiovascular risk profile" has been recommended by the 2020 European LeukemiaNet. However, the available literature and guidance on the use of ponatinib at low dosage are limited. The objective of this paper is to describe how we select ponatinib dosage for CML patients in chronic phase in our clinical practice based on the available evidence and our clinical experience. We propose dosing regimens for the optimal starting dose for six generic cases of CML patients in chronic phase eligible for the switch to ponatinib and provide an algorithm to guide ponatinib dosing during treatment.
Publication Date: 2021-04-03
Journal: Frontiers in oncology

Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia.
BCR-ABL1 plays a key role in the pathogenesis of chronic myeloid leukemia (CML), and it has been investigated as a druggable target of tyrosine kinase inhibitors (TKIs) over two decades. Since imatinib, the first TKI for anti-cancer therapy, was successfully applied in CML therapy, further generation TKIs and a novel allosteric inhibitor targeting the myristate binding site have been developed as alternative options for CML management. However, significant concerns regarding toxicity profiles, especially in long-term treatment, have emerged from TKI clinical data. Efforts to reduce adverse events and serious complications are warranted not only for survival, but also quality of life in CML patients. A better understanding of the mechanism of action will help to identify on- and off-target effects of TKIs, and guide personalized TKI drug selection in each individual CML patient. Herein, this review summarizes the biologic mechanism of BCR-ABL1 inhibition and differential target spectra, and related off-target effects of each TKI.
Publication Date: 2021-03-28
Journal: International journal of hematology

Third-line therapy for chronic myeloid leukemia: current status and future directions.
Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 fusion protein, formed by a translocation between chromosomes 9 and 22 that creates the Philadelphia chromosome. The BCR-ABL1 fusion protein is an optimal target for tyrosine kinase inhibitors (TKIs) that aim for the adenosine triphosphate (ATP) binding site of ABL1. While these drugs have greatly improved the prognosis for CML, many patients ultimately fail treatment, some requiring multiple lines of TKI therapy. Mutations can occur in the ATP binding site of ABL1, causing resistance by preventing the binding of many of these drugs and leaving patients with limited treatment options. The approved TKIs are also associated with adverse effects that may lead to treatment discontinuation in some patients. Efficacy decreases with each progressive line of therapy; data suggest little clinical benefit of treatment with a third-line (3L), second-generation tyrosine kinase inhibitor (2GTKI) after failure of a first-generation TKI and a 2GTKI. Novel treatment options are needed for the patient population that requires treatment in the 3L setting and beyond. This review highlights the need for clear guidelines and new therapies for patients requiring 3L treatment and beyond.
Publication Date: 2021-03-20
Journal: Journal of hematology & oncology

Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B.
Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 have revolutionized therapy for chronic myeloid leukemia (CML), paving the way for clinical development in other diseases. Despite success, targeting leukemic stem cells and overcoming drug resistance remain challenges for curative cancer therapy. To identify drivers of kinase-independent TKI resistance in CML, we performed genome-wide expression analyses on TKI-resistant versus sensitive CML cell lines, revealing a nuclear factor-kappa B (NF-κB) expression signature. Nucleocytoplasmic fractionation and luciferase reporter assays confirmed increased NF-κB activity in the nucleus of TKI-resistant versus sensitive CML cell lines and CD34
Publication Date: 2021-03-14
Journal: Oncogene

HHV8-Negative Effusion-Based Large B Cell Lymphoma Arising in Chronic Myeloid Leukemia Patients under Dasatinib Treatment: A Report of Two Cases.
Tyrosine kinase inhibitors (TKIs) are the treatment of choice for BCR-ABL1-positive chronic myeloid leukemia (CML). Although TKIs have substantially improved prognosis of CML patients, their use is not free of adverse effects. Dasatinib is a second generation TKI frequently associated with pleural effusion in up to 33% of patients. This results in symptoms as dyspnea, cough and chest pain that may require therapy discontinuation. In the present report, we describe two exceptional cases of HHV8-negative large B-cell effusion-based lymphoma (EBL) confined to the pleura, incidentally, diagnosed in patients presenting with dasatinib-related pleural effusion. One patient (case 1) is alive and is in remission at 17 months from large B-cell EBL diagnosis while unfortunately the other patient (case 2) died of progressive disease and COVID-19 pneumonia 16 months from large B-cell EBL diagnosis. These cases raise concern about a possible association between large B-cell EBL and dasatinib, and the different clinical outcome of the two cases poses a challenge in treatment decision. For this reason, we strongly recommend cytological investigation in patients with persistent/relapsing pleural effusion under dasatinib, primarily to validate its possible association with lymphoma development and to improve the knowledge about this entity.
Publication Date: 2021-03-07
Journal: Biology

Treatment-free remission and immunity in chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is caused by the reciprocal translocation t(9;22)(q34;q11), resulting in the BCR-ABL1 fusion gene. BCR-ABL1 tyrosine kinase inhibitors (TKIs) improve overall survival in patients with chronic phase CML (CML-CP). Approximately half of the patients who achieve a durable deep molecular response can achieve sustained treatment-free remission (TFR) after TKI discontinuation; thus TFR is now a therapeutic goal for most patients with CML-CP. Sensitive BCL-ABL1 transcript detection methods reveal that evidence of residual CML cells remains in patients who achieve sustained TFR, indicating that the host immune system protects against CML relapse. The human immune system is composed of innate and adaptive arms. Natural killer cells are major components of the innate immune system, while T cells are major components of the adaptive immune system. Myeloid-derived suppressor cells and regulatory T cells, both suppressors of the immune response, have important roles in the regulation of CML. Here, we review the current understanding of the immune response in CML, especially in TFR.
Publication Date: 2021-03-03
Journal: International journal of hematology

Axitinib in Ponatinib-Resistant B-Cell Acute Lymphoblastic Leukemia Harboring a T315L Mutation.
Adult acute lymphoblastic leukemia (ALL) with BCR-ABL1 rearrangement (Philadelphia chromosome, Ph) is a hematological aggressive disease with a fatal outcome in more than 50% of cases. Tyrosine kinase inhibitors (TKIs) targeting the activity of BCR-ABL1 protein have improved the prognosis; however, relapses are frequent because of acquired somatic mutations in the BCR-ABL1 kinase domain causing resistance to first, second and third generation TKIs. Axitinib has shown in vitro and ex vivo activity in blocking ABL1; however, clinical trials exploring its efficacy in ALL are missing. Here, we presented a 77-year-old male with a diagnosis of Ph positive ALL resistant to ponatinib and carrying a rare threonine to leucine (T315L) mutation on
Publication Date: 2021-01-10
Journal: International journal of molecular sciences

Dasatinib induces endothelial-to-mesenchymal transition in human vascular-endothelial cells: counteracted by cotreatment with bosutinib.
Adverse vascular events have become a serious clinical problem in chronic myeloid leukemia (CML) patients who receive certain BCR/ABL1 tyrosine kinase inhibitors (TKIs). Studies have shown that endothelial-to-mesenchymal transition (EndMT) can contribute to various vascular diseases. We investigated the effects of TKIs on the development of EndMT in human vascular-endothelial cells (VECs). Exposure of VECs to dasatinib, but not to other TKIs, produced a significant increase in the formation of spindle-shaped cells. This effect was accompanied by a significant increase in expression of the EndMT inducer transforming growth factor-β (TGF-β) and mesenchymal markers vimentin, smooth muscle alpha-actin, and fibronectin, as well as a significant decrease in expression of vascular-endothelial markers CD31 and VE-cadherin attributable at least in part to activation of ERK signaling. Inhibitors of TGF-β and ERK partially attenuated dasatinib-induced EndMT. Interestingly, bosutinib efficiently counteracted dasatinib-induced EndMT and attenuated dasatinib-induced phosphorylation of ERK. Taken together, these results show that dasatinib induces EndMT, which might contribute to the development of vascular toxicity, such as the pulmonary hypertension observed in CML patients receiving dasatinib. Bosutinib could play a distinct role in protecting VECs from EndMT.
Publication Date: 2021-01-05
Journal: International journal of hematology

[Treatments for Philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era].
The introduction of imatinib (IM) has led to a paradigm shift in the treatment strategy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). After introducing IM, second- and third-generation tyrosine kinase inhibitors (TKIs), which have stronger BCR-ABL1 inhibitory activity than IM, have appeared and their therapeutic results are beginning to be reported. However, to date, no comparison study between individual TKI and the current treatment strategy for Ph + ALL has been performed considering either a TKI-based regimen in induction followed by combination chemotherapy with a TKI or allogeneic hematopoietic stem cell transplantation (alloSCT). In the case of treating with ponatinib, it was suggested that the inclusion of alloSCT into the treatment strategy could be avoided. Because alloSCT has an appreciable treatment-related mortality rate and an upper age limit, the treatment strategy without alloSCT may remain mainstream in the future. Chemotherapy-free treatments, such as a TKI plus a monoclonal antibody or immunotherapy, are also expected to gain traction an alternate strategy and are now under investigation.
Publication Date: 2020-11-10
Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology

Surrogate Markers for Treatment-Free Remission in Patients With Chronic Myeloid Leukemia.
BCR-ABL1 tyrosine kinase inhibitors (TKIs) improve long-term survival of patients with chronic-phase (CP) chronic myeloid leukemia (CML). Recently, the treatment goal for patients with CML-CP became safe discontinuation of TKIs. Several clinical trials have shown that approximately half of patients who experience a durable deep molecular response during TKI treatment maintain molecular remission after discontinuation of TKIs. However, the factors responsible for successful treatment-free remission (TFR) remain unclear. This study reviews very recent TKI discontinuation studies, focusing on factors responsible for TFR in patients with CML-CP. Longer TKI treatment duration, time of deep molecular response, presence of withdrawal syndrome, deeper molecular response, lower Sokal score, interferon α treatment before TKI administration, and favorable natural killer or T-cell profiles may be associated with TFR. However, different study designs have generated inconsistent data. Further investigations are needed to identify factors that consistently favor achievement of TFR.
Publication Date: 2020-08-10
Journal: Clinical lymphoma, myeloma & leukemia

Allelic polymorphisms of
The development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) markedly improved the prognosis of patients with chronic myeloid leukemia (CML). Approximately 50% of patients who achieve deep molecular response (DMR) remain in treatment-free remission (TFR) even after discontinuation of TKIs. Although TKIs may achieve clinical "cure" after TKI treatment for specific periods, there are no reliable biomarkers for predicting the response to TKIs and the probability of TFR in CML. An increase in natural killer (NK) cells in the peripheral blood of TKI-treated CML patients is correlated with better outcomes, suggesting that TKIs induce antitumor NK cell immunity against CML cells. Killer immunoglobulin-like receptors (KIRs) are highly polymorphic NK cell receptors that play important roles in the regulation of immune responses. The identification of allelic polymorphisms of
Publication Date: 2020-07-28
Journal: Immunological medicine

Tyrosine Kinase Inhibitor Sequencing in Patients with Chronic Myeloid Leukemia.
The management of chronic myeloid leukemia (CML) has been revolutionized by the discovery of tyrosine kinase inhibitors (TKIs) against BCR-ABL1 oncogenic fusion protein. Imatinib, the first BCR-ABL1 TKI, was introduced into clinical practice in the early 2000s. In the following years, the so-called second-generation TKIs (2GTKIs)-dasatinib, nilotinib, and bosutinib were approved, initially for patients resistant to imatinib, and subsequently for front-line treatment. With multiple TKIs available, selection of first-line therapy is challenging. CML risk, patient characteristics and potential toxicities of different TKIs play a fundamental role, in particular when deciding between imatinib and 2GTKIs as frontline treatment. So, when deciding front-line therapy for a patient with CML in the chronic phase (CML-CP), clinicians must consider both the long-term outcomes, such as overall survival and progression-free survival, as well as safety, tolerance and possible treatment discontinuation. This paper offers a practical algorithmic approach for the sequential use of commercially available TKIs in patients with CML-CP along with the data available in the literature.
Publication Date: 2020-07-24
Journal: Oncology and therapy

Inhibition of ABL1 tyrosine kinase reduces HTLV-1 proviral loads in peripheral blood mononuclear cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.
Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML). ABL1 tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, and dasatinib, are used clinically for treating CML. To evaluate whether ABL1 is indeed important for HAM/TSP, we investigated the effect of TKIs on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKIs. Treating the PBMCs with nilotinib or dasatinib induced significant reductions in PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, ABL1 siRNA transfection reduced cell viability in HTLV-1-infected cell lines, but not in uninfected cell lines. A retrospective survey based on our clinical records found a rare case of HAM/TSP who also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is an important gene for the survival of HTLV-1-infected cells and that TKIs may be potential therapeutic agents for HAM/TSP.
Publication Date: 2020-07-16
Journal: PLoS neglected tropical diseases