[Cost-effectiveness analysis in the treatment of hematologic malignancies].

Recent advancements in treatment have improved the prognosis of hematologic malignancies. However, the increasing cost of therapeutic drugs has become an urgent issue. Cost-effectiveness analysis is performed using the incremental cost-effective ratio (ICER), a value calculated by dividing the incremental cost by the incremental quality-adjusted life year (QALY). The ICER must be compared with the willingness-to-pay (WTP) threshold, which differs between countries. Since the analysis should be made over a long time horizon, it is necessary to model and extrapolate the long-term outcomes of clinical trials to calculate cumulative costs and QALYs. This article discusses several approaches to cost-effectiveness analysis for chronic myelogenous leukemia, multiple myeloma, and CAR-T therapy. As even expensive treatments could be cost-effective if they provide long treatment-free survival, it is essential to judge cost-effectiveness by an appropriate method, rather than price alone.

[Allogeneic transplantation as a therapeutic option for atypical chronic myeloid leukemia].

Atypical chronic myeloid leukemia (aCML) is a rare disease classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Recent advances in gene mutational profiling have clarified the characteristics of aCML as a disease entity relative to other MDS/MPNs. Although some studies suggest the efficacy of DNA demethylating agents and tyrosine kinase inhibitors, data about these agents are limited due to the small number of patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is only therapeutic option that can provide durable remission for aCML and other MDS/MPNs. Retrospective studies from Europe and Japan revealed the clinical results of allo-HSCT for aCML. This review summarizes the pathogenesis of aCML and the development of allo-HSCT and other therapeutic options.

[Chronic myeloid leukemia: 2024 update on novel therapeutic strategies].

Many patients with chronic myeloid leukemia (CML) can now maintain response thanks to the advent of tyrosine kinase inhibitors (TKIs) and STAMP inhibitors, but adverse events associated with prolonged TKI therapy have become a problem. Adequate management of adverse events is key to successful treatment, as some can significantly impact the patient's prognosis. The goal of CML treatment was once to prevent acute transformation, but now that many patients achieve deep remission and long-term survival, the goal has shifted to achieving long-term treatment free remission (TFR). It is essential to carefully consider disease risk, patient background, and adverse events of each therapeutic agent in order to make the appropriate choice. This article reviews the treatment of chronic phase CML (CML-CP) as described in the 2023 edition of the Guidelines for Hematopoietic Tumors, focusing on treatment options for first-line CML-CP, dose optimization of ponatinib, outcomes with the new CML drug asciminib, and TFR.

Bilateral visual loss as the initial presentation of chronic myeloid leukemia: a case report.

Introduction: Chronic myeloid leukemia (CML) is the most common leukemia in adults. It can present with a wide variable range of symptoms and signs related to the phase of the disease. Ophthalmic manifestations as the first presentation of CML are unique, although they can occur during any stage of the disease. Ocular lesions in CML patients may be asymptomatic, so all patients should undergo an eye evaluation at the initial diagnosis. Case presentation: The authors report a case of a 17-year-old Syrian male who initially presented with progressive loss of vision, fatigue, and abdominal pain. Clinical examination showed bilateral retinal aneurysm hemorrhage, jaundice, and splenomegaly. Bone marrow biopsy results were consistent with the diagnosis of CML returning to AML. The patient was treated with intensive chemotherapy and then prepared for hematopoietic transplantation. Discussion: CML can present with variable symptoms and signs, but the ophthalmic manifestations are uncommon. Ophthalmic problems occur either from infiltration of neoplastic cells or from secondary causes, like thrombocytopenia, leukocytosis, hyperviscosity syndrome, or leukoembolization. In the literature, only some case reports presented eye involvement in CML as the first manifestation. Conclusion: Although this is a rare presentation of CML, we believe that it should be taken into consideration when managing these situations to obtain the right diagnosis and better treatment results. Collaboration between hematologists and ophthalmologists is necessary in deciding the treatment. Acute myeloid leukemia needs immediate medical attention and different treatment from CML.

Dasatinib-Induced Bilateral Chylothorax: A Case Report.

Dasatinib, a BCR-ABL tyrosine kinase inhibitor, is used in the management of Philadelphia-positive chronic myeloid leukemia (CML). Several adverse complications of this targeted immunotherapy have been reported. This case report focuses on a 79-year-old female who presented with acute dyspnea and generalized chest pressure while undergoing management with this specific tyrosine kinase inhibitor. Bilateral chylothorax was diagnosed with the aid of imaging, laboratory studies, and diagnostic thoracentesis. No other risk factors, including trauma, lung malignancies, or congenital anomalies, were detected in this patient. Since no other etiologies for the development of chylothorax were identified, it was concluded that dasatinib therapy was the inciting factor. Dasatinib was discontinued and bosutinib was initiated. A low-fat diet was prescribed, which the patient was amenable to. Six months later, the patient remained stable with no recurrence of chylothorax. The mechanism of dasatinib-induced chylothorax is currently under investigation. The purpose of this report is to raise awareness about dasatinib-induced chylothorax, aid in identifying predisposing risk factors, and enhance understanding of the proper management of this rare complication.

Sustained antiviral response against in vitro HIV-1 infection in peripheral blood mononuclear cells from people with chronic myeloid leukemia treated with ponatinib.

HIV-1 infection cannot be cured due to long-lived viral reservoirs formed by latently infected CD4+ T cells. "Shock and Kill" strategy has been considered to eliminate the viral reservoir and achieve a functional cure but the stimulation of cytotoxic immunity is necessary. Ponatinib is a tyrosine kinase inhibitor (TKI) clinically used against chronic myeloid leukemia (CML) that has demonstrated to be effective against HIV-1 infection in vitro. Several TKIs may induce a potent cytotoxic response against cancer cells that makes possible to discontinue treatment in people with CML who present long-term deep molecular response. In this longitudinal study, we analyzed the capacity of ponatinib to induce an antiviral response against HIV-1 infection in peripheral blood mononuclear cells (PBMCs) obtained from people with CML previously treated with imatinib for a median of 10 years who changed to ponatinib for 12 months to boost the anticancer response before discontinuing any TKI as part of the clinical trial NCT04043676. Participants were followed-up for an additional 12 months in the absence of treatment. PBMCs were obtained at different time points and then infected in vitro with HIV-1. The rate of infection was determined by quantifying the intracellular levels of p24-gag in CD4+ T cells. The levels of p24-gag+ CD4+ T-cells were lower when these cells were obtained during and after treatment with ponatinib in comparison with those obtained during treatment with imatinib. Cytotoxicity of PBMCs against HIV-infected target cells was significantly higher during treatment with ponatinib than during treatment with imatinib, and it was maintained at least 12 months after discontinuation. There was a significant negative correlation between the lower levels of p24-gag+ CD4+ T-cells and the higher cytotoxicity induced by PBMCs when cells were obtained during and after treatment with ponatinib. This cytotoxic immunity was mostly based on higher levels of Natural Killer and Tγδ cells seemingly boosted by ponatinib. In conclusion, transient treatment with immunomodulators like ponatinib along with ART could be explored to boost the antiviral activity of cytotoxic cells and contribute to the elimination of HIV-1 reservoir.

Distinct clinical profiles and patient outcomes in aCML and CNL.

The classification of atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) as a single disease entity remains a topic of debate. To elucidate the characteristics of both entities, this retrospective cohort study was conducted, encompassing 36 cases of aCML and 18 cases of CNL. We discovered that aCML and CNL presented distinct blood counts, genetics, molecular profiles and outcomes. Specifically, hemoglobin levels (P < 0.001) and platelet counts (P < 0.001) were significantly lower in aCML cases than in CNL cases, with no significant difference in mean white blood cells (P = 0.637). The proportion of abnormal karyotypes was higher in aCML cases compared with CNL cases (P = 0.010). Notably, we found that aCML and CNL showed distinct gene expression profiles by transcriptome sequencing technology. The median follow-up duration for the entire cohort was 8 months (rang 0.4 to 36.6 months), and the median overall survival (OS) was significantly shorter in aCML cases (7.3 months, 95%CI 5.4 to 20.5 months) than in CNL cases (median OS not reached). The one-year OS rate for aCML patients was 31.0% (9/29), compared to 92.9% (13/14) for CNL patients. In conclusion, our study supports the notion that aCML and CNL are indeed distinct disease entities characterized by unique hematological features and clinical outcomes.

Morphology, Morphometry, and Immunohistochemical Profile of Megakaryocytes and Bone Marrow Microenvironment in Disease Progression and Therapy Resistance in Chronic Myeloid Leukemia.

Background Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML) since the beginning of the century. However, resistance to therapy and the progression of disease tend to occur in certain patients. The bone marrow microenvironment may play a role in the disease outcome. Megakaryocytes have multiple roles in the regulation and maintenance of the hematopoietic stem cell microenvironment. In the current study, we evaluated the association of megakaryocyte morphology, morphometry, and microenvironment with disease progression and therapy resistance in CML. Methodology Megakaryocyte morphology and morphometry were analyzed and compared between the different phases (chronic and advanced) at diagnosis in 150 cases of BCR-ABL-positive CML. All CML-CP patients (n = 119) were followed up on tyrosine kinase inhibitor therapy for a minimum of 15 months and classified based on their treatment outcome as a response, resistance to therapy, or progression of disease based on standard criteria. Immunohistochemistry on a bone marrow trephine biopsy was done for vascular endothelial growth factor (VEGF), FOXP3, CD150, CD48, CD44, osteopontin, CXCL12, N-cadherin, PDL-1, and IL-7, and their expression on megakaryocytes and their association with treatment outcome was evaluated. Results The morphology and morphometry of megakaryocytes showed a heterogeneous population in CML. Morphology and morphometric parameters, when compared between the chronic and advanced phases of disease at diagnosis, did not show any statistical difference. Megakaryocytes were variably positive for VEGF, FOXP3, CD150, CD48, osteopontin, N-cadherin, CXCL12, CD44, PDL-1, and IL-7. However, only CD44-positive megakaryocytes were statistically associated with the treatment outcome. The patients with a higher expression of CD44 megakaryocytes progressed to the advanced phase of the disease during therapy compared to those who responded. Conclusion Megakaryocyte morphology and morphometry were heterogeneous in CML; however, they did not show any significant difference with either the phase of the disease or with treatment outcomes. Among the various immunohistochemical markers of the microenvironment, only CD44-positivity on megakaryocytes was associated with poor treatment outcomes.

Celastrol induces DNA damage and cell death in BCR-ABL T315I-mutant CML by targeting YY1 and HMCES.

BACKGROUND: Chronic myeloid leukemia (CML) is driven primarily by the constitutively active BCR-ABL fusion oncoprotein. Although the development of tyrosine kinase inhibitors has markedly improved the prognosis of CML patients, it remains a significant challenge to overcome drug-resistant mutations, such as the T315I mutation of BCR-ABL, and achieve treatment-free remission in the clinic. PURPOSE: The identification of new intervention targets beyond BCR-ABL could provide new perspectives for future research and therapeutic intervention. A network pharmacology analysis was conducted to identify the most promising natural product with anti-CML activity. Celastrol was selected for further analysis to gain insights into its mechanism of action (MoA), with the aim of identifying potential new intervention targets for BCR-ABL T315I-mutant CML. METHODS: Transcriptomic and proteomic analyses were conducted to systematically investigate the molecular MoA of celastrol in K562T315I cells. To identify the target proteins of celastrol, mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) was carried out, followed by validations with genetic knockdown and overexpression, cell proliferation assay, comet assay, Western blotting, celastrol probe-based in situ labeling and pull-down assay, molecular docking, and biolayer interferometry. RESULTS: Our multi-omics analyses revealed that celastrol primarily induces DNA damage accumulation and the unfolded protein response in K562T315I cells. Among the twelve most potential celastrol targets, experimental evidence demonstrated that the direct interaction of celastrol with YY1 and HMCES increases the levels of DNA damage, leading to cell death. CONCLUSION: This study represents the first investigation utilizing a proteome-wide label-free target deconvolution approach, MS-CETSA, to identify the protein targets of celastrol. This study also develops a new systems pharmacology strategy. The findings provide new insights into the multifaceted mechanisms of celastrol and, more importantly, highlight the potential of targeting proteins in DNA damage and repair pathways, particularly YY1 and HMCES, to combat drug-resistant CML.

Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia.

BACKGROUND: In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis. METHODS: Peripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman's rho correlation test, and the Kaplan-Meier method were used for statistical analysis. RESULTS: The aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1IS. CONCLUSIONS: Our study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.

Imatinib Adherence and Persistence in Patients with Chronic Myeloid Leukemia in Belgium: Evidence from Real-World Data.

Purpose: Imatinib adherence and persistence are key components of the successful treatment of Chronic Myeloid Leukemia (CML). In Belgium, there is no study assessing these behaviors at a national level. Our study aimed to provide the first nationwide measure and to identify associated pharmacy-based predictors (age, gender, comorbidities). We also assessed mortality and transplantation incidence according to adherence status. Methods: Based on medico-administrative database linkage, we identified a retrospective Belgian cohort of 1194 patients diagnosed with CML between 2004 and 2016 and treated with imatinib. Adherence was measured over 24 months, considering the proportion of days covered (PDC). Persistence was measured as the time until discontinuation (gap of ≥90 days). Multivariable Poisson regression models with robust standard error were conducted to identify predictors associated with adherence (≥90% PDC). To identify factors associated with persistence, a multivariable Cox regression was performed. Results: At six months, 60.3% of patients were adherent, declining to 41.5% at 12 months, and to 30.1% at two-year follow-up (n=998). Adherence was greater at a younger age (eg 31-40 years vs ≥75 years, adjusted prevalence ratio (aPR) 1.73; 95% confidence interval (CI): 1.09-2.77) and among patients with no comorbidity (0 vs ≥2 comorbidities (aPR 1.56; 95% CI: 1.11-2.19). The median persistence was 334.5 days (Q1:200-Q3:505.5); persistence at 24 months was 83.6% (n=998). Only age was associated with higher risk of discontinuation, with adjusted hazard ratio (aHR) of 6.05 for patients ≥75 years (95% CI: 5.52-6.58). Transplants and deaths mainly occurred in patients defined as non-adherent at 24 months. Conclusion: This Belgian nationwide representative study revealed a critical low level of imatinib adherence, which decreased over time even though persistence was high at six months. We pinpointed pharmacy-based predictors that were easily identifiable by health care stakeholders in order to undertake interventions to improve adherence.

The introduction of imatinib, a new oral anticancer medication, has transformed chronic myeloid leukemia (CML) from a fatal disease to a chronic disease. However, the success of imatinib partly depends on how long a patient continues to take it (persistence) and the extent to which they take imatinib as prescribed (adherence). Over a 24-month follow-up period, this study aimed to provide an assessment of imatinib adherence and persistence for the first time and to identify associated risk factors. Using pharmacy dispensing data, our study revealed that whilst very few CML patients discontinued imatinib, a considerable proportion struggled to adhere to imatinib recommendations, with a decreasing rate of adherence and persistence over time. We have identified some demographic and clinical characteristics associated with higher risk of poor adherence and early discontinuation. The current study's findings will help healthcare professionals to screen adherence behaviors prospectively and design specific interventions to maintain long-term optimal adherence to imatinib.

Pharmaceutical inhibition of BCL6 ameliorates resistance to imatinib in chronic myeloid leukemia.

The tyrosine kinase inhibitors (TKIs) have improved overall survival of CML (chronic myeloid leukemia) patients and allow them to experience normal life expectancy. However, relapse and drug resistance remain the main challenges in the clinical treatment of CML. The B-cell lymphoma 6 (BCL6) is essential to regulation of multiple function such as immune response and lymphomagenesis in lymph node germinal cells. Recent studies have shown that BCL6 is required for the maintenance of leukemia stem cells in CML, but the expression of Bcl-6 in response to Imatinib and the underlying mechanism are still unclear. Here, we found that BCL6 is expressed at high levels in primary CML bone marrow samples and CML TKI-resistance cell lines. CML cells with higher levels of BCL6 were generally sensitive to treatment with BCL6 inhibitors, BI-3812. Treatment of CML cells with BCL6 inhibitor and TKIs suggested enhanced anti-leukemia activity. In summary, our findings suggest BCL6 as a therapeutic target for the treatment of CML.

Advancements in Chronic Myeloid Leukemia detection: Development and evaluation of a novel QCM aptasensor for use in clinical practice.

Oncological diseases represent a significant global health challenge, with high mortality rates. Early detection is crucial for effective treatment, and aptamers, which demonstrate superior specificity and stability compared to antibodies, offer a promising avenue for diagnostic advancement. This study presents the design, development and evaluation of a quartz crystal microbalance (QCM) sensor functionalized with the T2-KK1B10 aptamer for the sensitive and specific detection of Chronic Myeloid Leukemia (CML) K562 cells. The research focuses on optimizing the biorecognition layer by adjusting the aptamer conditions, demonstrating the sensor's ability to detect these CML cells with high specificity and sensitivity. The aptamer-modified QCM sensor operates on the principle of mass change detection upon binding of target cells. By employing the Langmuir isotherm model, the performance of the sensor was optimized for the capture of CML cells from biological samples with LOD of 263 K562 cells. The sensor was also successfully regenerated multiple times without sensitivity loss. Validation of the sensor's performance was conducted under controlled laboratory settings, followed by extensive testing utilizing human lyophilized plasma and clinical samples from patients. The sensor exhibited high sensitivity and specificity in the detection of CML cells within clinical specimens, thereby illustrating its potential for practical clinical deployment. This research presents a novel approach to the early diagnosis of CML, facilitating timely intervention and enhanced patient outcomes. The developed aptasensor demonstrates potential for broader application in cancer diagnostics and personalized medicine.

Imatinib­induced gynecomastia: A case report.

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the unregulated and abnormal proliferation of both mature and immature granulocytes, which results in the proliferation of peripheral blood leukocytes. Imatinib, a tyrosine kinase inhibitor, is the first-line treatment for patients diagnosed with chronic myeloid leukemia. However, despite its favorable safety profile, imatinib use is associated with a number of side effects. Gynecomastia is a rare adverse effect of imatinib treatment and may be associated with an imbalance in sex hormones. The present study reports the case of a patient with chronic myeloid leukemia diagnosed with gynecomastia after imatinib treatment. The aim of the present report was to highlight to clinicians this adverse reaction to imatinib treatment and investigate a treatment strategy with fewer side effects.

Clinical efficacy and safety of first-line nilotinib or imatinib therapy in patients with chronic myeloid leukemia-Nationwide real life data.

BACKGROUND: To evaluate the outcomes of first-line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML-CP) in real-world clinical practice. METHODS: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. RESULTS: Nilotinib-treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib-treated patients. However, there was no significant difference in 5-year overall survival (OS) or progression-free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib-treated patients had a higher failure-free survival (FFS) and event-free survival (EFS) than imatinib-treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). CONCLUSIONS: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort.

Chronic myeloid leukemia diagnosed from the course of diabetic retinopathy.

We report a case of chronic myeloid leukemia (CML), which was diagnosed during the management of proliferative retinopathy (PR) in a patient with type I diabetes mellitus due to the fulminant nature of the PR. This case highlights the importance of vigilance on the part of the ophthalmologist in the diagnosis of co-existing systemic disorders, notably hematological malignancy, which aggravates the posterior segment vasculopathy of the eye and the management of which is crucial for the patient. We also describe a short literature review on the clinical features, mechanism of the posterior segment vasculopathy of the eye, and management of PR co-existing in a patient with CML.

Unprecedented Megakaryocytic Blast Phase Transformation in Chronic Myeloid Leukemia After 16 Years of Tyrosine Kinase Inhibitor Therapy.

We report the case of a 51-year-old Japanese man with chronic myeloid leukemia (CML) initially diagnosed in the chronic phase. For 16 years, the patient maintained chronic phase (CP) under treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib, and bosutinib, none of which resulted in ABL1 mutations. However, despite long-term disease stability, the patient experienced an abrupt progression to the megakaryocytic blast phase (MBP), a rare and aggressive form of CML. In response to this progression, ponatinib, a third-generation TKI, was introduced as a fourth-line therapy. Remarkably, within 7 months of initiating ponatinib, the patient achieved a deep molecular response (DMR), evidenced by a reduction in BCR::ABL1 transcript levels to undetectable levels (MR5.0). This molecular remission enabled the patient to proceed with an allogeneic bone marrow transplantation from a human leukocyte antigen (HLA) 8/8-allele-matched unrelated donor. Post-transplantation, the patient has maintained DMR for 14 months without recurrence, despite the challenges posed by graft-versus-host disease. This case illustrates the critical role of third-generation TKIs like ponatinib in managing advanced CML phases, especially when previous therapies fail. It also emphasizes the necessity of vigilant long-term monitoring during the chronic phase to detect and address any signs of disease progression promptly.

Chronic Myeloid Leukemia Unveils Its Dark Side: A Rare Case of Megakaryocytic Blast Crisis.

Chronic myeloid leukemia (CML) can progress from a chronic phase (CP) to an accelerated phase (AP) or an acute leukemia-like blastic phase (BP). However, transformation into a megakaryoblastic phase is very rare, and such a progression is clinically significant due to its poor prognosis and resistance to standard tyrosine kinase inhibitors (TKIs). This report discusses a case of CML that progressed to a megakaryoblastic phase and the patient's death within a month despite receiving one cycle of daunorubicin, cytarabine, and TKI chemotherapy. A 39-year-old female with CML (CP) initially achieved hematological remission with nilotinib but later presented with B symptoms and cytopenias indicative of disease progression. A complete diagnostic workup was performed, including blood counts, bone marrow examination, flow cytometry, fluorescence in-situ hybridization (FISH), and cytogenetic testing. Peripheral blood and bone marrow evaluation confirmed blast crisis with 84% medium to large-sized blasts with basophilic cytoplasm and cytoplasmic blebs. The blasts were positive for CD41 and CD61 by immunohistochemistry (IHC). The blasts also expressed CD45 (dim), CD34, CD33, CD117, CD41, and CD61 by flow cytometry. While BCR-ABL1 positivity is typically associated with CML (90-95%), the additional findings point towards a transformation to acute megakaryoblastic leukemia (AMKL or AML-M7). The rare instance of CML's transformation to AMKL highlights the need for megakaryocytic markers in diagnostic panels to ensure accurate diagnosis and timely, tailored therapies for improved outcomes.