Chronic myeloid leukaemia (CML), a distinct myeloproliferative neoplasm, results from the malignant reprogramming of haematopoietic stem cells (HSCs) into leukaemia stem cells (LSCs), primarily driven by breakpoint cluster region and Abelson (BCR-ABL1) fusion oncogene. Although the advent of tyrosine kinase inhibitors (TKIs) has significantly transformed clinical management, leading to improved patient survival and quality of life, sustained treatment-free remission (TFR) remains achievable in only a minority of patients. This limitation is largely attributable to the persistence of LSCs and the development of resistance mechanisms. Emerging evidence indicates that LSCs evade TKI-induced apoptosis through aberrant expression of specific cell-surface markers, dysregulated intracellular signalling pathways, and extensive epigenetic alterations. This review examines recent advancements in CML therapy, with a focus on these novel therapeutic targets. It highlights the pivotal role of LSCs in disease progression and relapse, evaluates potential molecular and epigenetic regulators as new targets for intervention, and supports the development of combination treatment strategies to improve TFR rates and move towards curative outcomes.

Five years after the first readout of the ASCEMBL trial, asciminib evidence has rapidly expanded across the chronic myeloid leukemia (CML) treatment landscape. Subsequent studies and growing real-world experience have also clarified its efficacy and tolerability in earlier treatment lines. As the first allosteric inhibitor targeting the BCR::ABL1 myristoyl pocket, asciminib provides a mechanistically distinct approach that may reduce cross-resistance and toxicity associated with ATP-competitive TKIs. At a time when treatment goals in CML emphasize long-term tolerability, quality of life, and the potential for treatment-free remission (TFR), asciminib's unique molecular and clinical profile justify its inclusion in CML treatment considerations. In this expert opinion review, we synthesize emerging clinical and real-world evidence for asciminib and discuss practical considerations for its integration into contemporary CML management, including its potential im-plications for TFR eligibility. We also explore the role of next-generation sequencing in detecting salvageable resistance mutations, the prognostic significance of co-mutations such as ASXL1, and the concept of mutation-guided treatment sequencing. Collectively, these data position asciminib as an established later-line therapy and an emerging frontline option, with the potential to improve long-term treatment sustainability through favorable tolerability and early molecular response kinetics.

Duffy-null-associated neutrophil count (DANC) refers to a below-normal absolute neutrophil count (ANC < 1.5 × 10[3]/L), present most commonly in African American individuals. Neutropenia is a result of a lack of Fya and Fyb antigens on red blood cells. These patients do not have an increased risk of infection and may have an ANC < 1.5 × 10[3]/L at baseline. This unique case presents Duffy-null-associated neutropenia in the setting of chronic myeloid leukemia (CML). A 64-year-old African American female presented to the emergency department on May 17, 2021, for fatigue and was found to have a white blood cell (WBC) count of 65.3 × 10[9]/L. Hematology and oncology referral led to a diagnosis of CML. Subsequently, she began treatment with imatinib (Gleevec) 400 mg daily. One month into treatment, she was neutropenic, with an ANC of 0.6 × 10[3]/L. For the next several years, this patient repeatedly had treatment holds and dose reductions in response to recurrent neutropenia. When BCR-ABL1 transcript level continued to increase, indicating poor treatment response, she was referred to Medical University of South Carolina (MUSC). After several treatment changes due to adverse effects, she began treatment with asciminib 80 mg daily. BCR-ABL1 transcript level with asciminib was consistently below 0.1%, indicating successful treatment response. Despite this milestone, she continued to have episodes of neutropenia, prompting a check for Duffy antigen presence. Testing confirmed the lack of Fya and Fyb antigens, indicating Duffy-null status. This case demonstrates the importance of identifying Duffy-null individuals. Despite achieving major molecular response, the patient had persistent neutropenia, leading to the investigation of Duffy-null status. It is hypothesized that underlying Duffy-null status may have caused neutropenia, rather than an adverse reaction to treatment. Early detection of Duffy-null status can prevent dose reductions in therapy and delayed remission. Particularly with African American patients, a better framework for addressing Duffy-null neutropenia may benefit long-term outcomes in the setting of cancer therapy.

Ataxia Telangiectasia Mutated (ATM), a central kinase in the DNA damage response, is recurrently altered across these disorders, including myelodysplastic neoplasms (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), yet its clinical significance remains underrecognized. We conducted a PROSPERO-registered systematic review (CRD420251142673) to evaluate the prognostic and biological impact of ATM alterations in MDS, AML, and MPN. Ten studies met inclusion criteria. In MDS, ATM alterations showed consistent downregulation, hypermethylation, and a predominance of oncogenic missense mutations, with methylation significantly enriched in cases progressing to AML. In AML, reduced ATM gene expression, often driven by miR-100 or miR-181a, was associated with increased blast proliferation, while the ATM genetic variant rs3092856 correlated with chemoresistance and inferior survival. Evidence in MPN/CML, although limited, suggests that ATM polymorphisms, such as rs228593, rs3092856 (C4138T), -5144A>T (rs228589), c.5753G>C, c.346A>G, c.4060C>A, and the germline variant L2307F, contribute to disease susceptibility and adverse prognostic stratification. Collectively, current evidence supports ATM alterations as clinically relevant biomarkers in myeloid malignancies, although their functional role in disease pathogenesis remains incompletely understood.. Rather than establishing ATM merely as a prognostic marker, future efforts should prioritize the characterization of ATM-related therapeutic vulnerabilities and integrate ATM status into treatment-oriented molecular panels to guide precision-based interventions in myeloid diseases.

Intracranial myeloid sarcoma complicating chronic myeloid leukemia (CML) is exceptional; when its cerebrospinal-fluid profile simultaneously mimics tuberculous meningitis (TBM), the diagnostic trap becomes fatal. A 27-year-old postpartum woman with Ph[+] CML, initially presenting in B-cell acute lymphoblastic leukemia lymphoid blast crisis, developed rapidly progressive posterior-fossa syndrome following peripartum tyrosine kinase inhibitor (TKI) discontinuation. CSF revealed lymphocyte-predominant pleocytosis, hypoglycorrhachia, hyperproteinorachia, and adenosine deaminase 33 U/L, with negative CBNAAT, malignant cytology, and flow cytometry; BCR-ABL1 P210 registered an International Scale of 49.196%. Contrast-enhanced MRI demonstrated a dural-based, homogeneously enhancing, diffusion-restricting cerebellopontine mass with pachymeningeal involvement, consistent with granulocytic sarcoma. Death from tonsillar herniation occurred within one week, before tissue confirmation. Three imperatives emerge: CSF adenosine deaminase elevation lacks specificity for TBM in hematological malignancy; Ph[+] CML can undergo myeloid CNS relapse following peripartum TKI cessation; and a posterior-fossa dural mass in leukemia demands urgent tissue diagnosis.

Allogeneic hematopoietic cell transplantations (allo-HCT) is a procedure with long history and well-documented efficacy in treating various malignant and non-malignant diseases of the hematopoietic system. While there is a potential for late complications even over 10 years following allo-HCT, the data on longer observations are limited due to loss in follow-up, personnel and organizational changes in transplant centers, and focusing on new promising therapies instead of HCT. The study aimed to evaluate 15- and 20-year overall and progression-free survival of allo-HCT recipients in our center. During the inclusion period from 1999 to 2014, we identified 269 allo-HCT recipients. Survival analyses were performed using Kaplan-Meier curves, the Cox proportional hazards model, and the log-rank test. First, we evaluated 15- and 20-year survival rates for the entire cohort of allo-HCT recipients from matched related donor (MRD) and matched unrelated donor (MUD). Then we performed similar analyses for allo-HCT recipients due to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic neoplasms (MDS), non-Hodgkin lymphomas (NHL), and severe aplastic anemia (SAA). It was confirmed that survival benefit continues also during long-term observation. Notably, the plateau effect of PFS was often observed over 20 years following allo-HCT, implying the ability to cure in a relatively large group of patients with otherwise incurable diseases.

Chronic myeloid leukemia (CML) is driven by constitutive BCR-ABL1 activity and remains clinically challenging due to disease persistence and resistance to tyrosine kinase inhibitors (TKIs). SIRT1, a NAD[+]-dependent deacetylase, has been implicated in leukemic cell survival and chemoresistance through negative regulation of p53. In this study, we evaluated the antileukemic effects of the Sechium hybrid H387 extract and its impact on the SIRT1-p53 signaling axis in K562 CML cells. Cell proliferation was assessed using a crystal violet assay, while gene and protein expression were analyzed by RT-qPCR, immunofluorescence, and flow cytometry. Apoptosis was determined by Annexin V/7-AAD staining. The extract significantly inhibited K562 cell proliferation and downregulated SIRT1 expression, reducing its nuclear localization. These effects were associated with increased p53 acetylation at lysine 382 (Ac-K382-p53) and enhanced apoptosis. Notably, a higher percentage of apoptotic cells was observed following extract treatment than with imatinib under the experimental conditions used, although the two agents have distinct mechanisms of action. These findings suggest that the antileukemic activity of Sechium hybrid H387 extract is associated with modulation of the SIRT1-p53 axis and induction of apoptosis in K562 cells.

Tyrosine kinase inhibitors (TKIs) improve survival for people with chronic myeloid leukemia (CML) but may cause adverse events (AEs) that impair quality of life (QoL). Adults with CML receiving first- or second-line TKI therapy in the United States (US) completed validated questionnaires to assess AEs (PRO-CTCAE), QoL (PROMIS Global Physical Health [GPH] and Global Mental Health [GMH]), and work productivity and activity impairment (WPAI:SHP). Of 271 participants, 76.4% experienced ≥1 AE (median 3 [range 0-14]), with the most common being fatigue (53.9%), pain (44.3%), and gastrointestinal symptoms (36.9%). Mean (SD) GPH and GMH T-scores were worse than general population averages (50) at 42.6 (7.0) and 44.4 (7.7), respectively. Mean (SD) activity impairment was 37.3% (24.6). Chronic AEs were associated with worse GPH/GMH T-scores and activity impairment (p < 0.05). The findings demonstrate the relationship between TKI-related AEs and QoL for US patients and the need for improved management strategies.

Anesthetic management of pregnant patients with chronic myeloid leukemia (CML) is complicated by concerns that neuraxial techniques could theoretically introduce leukemic cells into the central nervous system. Evidence guiding anesthetic decisions in chronic-phase CML without circulating blasts is limited. We describe two pregnant patients with CML in whom anesthetic management was individualized based on disease status and obstetric risk. Systemic analgesia was chosen when molecular relapse raised concern for occult blasts, whereas spinal anesthesia was performed in deep molecular remission when maternal comorbidities increased the risk of general anesthesia. Both patients had uncomplicated deliveries, with molecular remission confirmed at 1-year follow-up.