ABL1 fusion

This case adds to the limited literature reporting cup-like nuclear morphology in B-ALL, which is typically associated with varied cytogenetic abnormalities, including BCR::ABL1 fusion and hyperdiploidy [3, 4]. The findings emphasize the critical role of FCI and molecular studies in distinguishing AML from B-ALL or mixed phenotype acute leukemias.

Hence, this minimalistic approach may be further validated in future studies. The online version contains supplementary material available at 10.1007/s12288-025-01968-2.

KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential, decreased imatinib sensitivity, and reduced apoptosis...KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2 (SMAD2); however, the latter impaired transforming growth factor-beta (TGF-β)-mediated SMAD2/3 activation while enhancing STAT3 phosphorylation. This study demonstrates the biological and functional importance of KLC2 mutation in CML cells, potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.

CD97, CD73, CD86, and CD58 are the best amongst newer markers in B-ALL MRD assessment. Our findings support integrating these into MRD panels to enhance post-therapy MRD detection, thus improving prognostication and guiding treatment decisions.

The incorporation of gene expression analysis, with confirmation using orthogonal methods, may help improve diagnostic yield. Developing practice guidelines will help harmonise reporting content and minimise interlaboratory variations.

These insights reveal potential therapeutic strategies aimed at disrupting the leukemic stem cell supportive niche to achieve more effective eradication of resistant clones. Understanding the complex interplay between leukemic stem cells and their microenvironment is crucial for developing targeted treatments that can overcome resistance and achieve long-term remission in patients with chronic myeloid leukemia.

At present, there is no established consensus on the treatment of Ph + MPAL, and reports on cases with the atypical e13a3 BCR::ABL1 fusion are particularly scarce. This finding will bring new insights and references for the diagnosis and treatment of Ph + MPAL.

We will discuss how these factors may help shape therapeutic choices. Finally, we will highlight innovative research avenues aiming at improving prognostication of CML.

Post-transplant TKI maintenance improved outcomes in BCR-ABL+ BCP-ALL. EudraCT: 2012-0032-22; ClinicalTrials.gov: NCT01949129.

Moreover, epigenetic silencing of miR-203 enhances BCR::ABL1 expression, further contributing to TKI resistance. These small regulatory RNAs consequently act for promising candidates both as therapeutic targets and as prognostic biomarkers, with the potential to fill treatment gaps that persist even in the TKI era.

Through a systematic review of published e8a2 BCR::ABL1 cases, we summarized the classification, treatment outcomes, and prognostic characteristics associated with this rare genotype. This analysis aims to provide additional evidence to facilitate improved diagnosis and therapeutic strategies for e8a2-positive CML patients.

Notably, the presence of NUP214::ABL1 identified a clinically actionable target, supporting the use of tyrosine kinase inhibitors (TKIs) such as imatinib. This case underscores the critical role of integrated sequencing approaches in identifying cryptic genetic alterations in B-ALL for precise classification of oncogenic drivers and for targeted therapeutic strategies to improve patient outcomes.