BCR (BCR Activator Of RhoGEF And GTPase)

Second-generation and third-generation TKIs further improved outcomes by targeting most imatinib-resistant mutations, with ponatinib-based regimens achieving deep molecular responses and long-term survival in most patients. Concurrently, immunotherapies like blinatumomab and CAR-T cells have enabled potent chemotherapy-free strategies, yielding high molecular response rates and challenging the necessity of allo-HSCT for all patients. Current evidence supports reserving allo-HSCT for high-risk patients, while those with sustained minimal residual disease (MRD) negativity may be cured with TKI and immunotherapy alone. Future progress hinges on optimizing combinations, integrating novel agents like asciminib and venetoclax, and leveraging MRD and genomic profiling for precision medicine.

P2, N=80, Not yet recruiting, University of Alberta | Initiation date: Mar 2026 --> Jul 2026

Notably, genetic or pharmacological inhibition of PELI1 effectively suppresses the proliferation of both tyrosine kinase inhibitors (TKIs)-sensitive and TKI-resistant CML cells, as well as Leukemia stem cells (LSCs), which consequently ameliorates the disease burden and progression of CML. Collectively, our findings demonstrated that targeting PELI1 is a promising therapeutic strategy for CML that can overcome TKI resistance and eliminates LSCs.

P2, N=17, Active, not recruiting, Baylor College of Medicine | N=100 --> 17 | Recruiting --> Active, not recruiting

P2, N=406, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

It also focuses on bypass pathways, the B-cell/CLL lymphoma 2 family, tumor suppressor genes, microRNAs, and molecular chaperones as independent resistance mechanisms. Furthermore, the potential for combination therapies targeting these resistance mechanisms is discussed, anticipating further advances in research aimed at overcoming TKI resistance in CML.

While JAK2 V617F mutation was associated with distinct hematologic profiles, it was not independently linked to thrombotic risk. These findings highlight the significance of clinical comorbidities and hematologic parameters in thrombotic event occurrences in MPN patients.

Circulating CD34+CD38-h-MICL+ cells represent a promising biomarker; their quantification may aid in subclassification, particularly in distinguishing prefibrotic MF from ET, and may serve as a potential target for future therapeutic strategies. Further validation in larger cohorts is warranted.

Collectively, these findings suggest that MUC3A P258S acts as a potential candidate biomarker of CML progression and influences therapeutic response, highlighting Capmatinib and related inhibitors as candidates for drug repurposing in hematological malignancies. To our knowledge, this is the first report implicating MUC3A in leukemia biology, extending its role beyond epithelial cancers.

In this study, we present a case of BCR-ABL(+) AML that was treated with a TKI in combination with chemotherapy to induce remission, followed by allogeneic hematopoietic stem cell transplantation (Allo-HSCT). We also review the relevant literature to shed light on treatment strategies for BCR-ABL(+) AML and provide strong support for Allo-HSCT as a therapeutic option for this subtype.

Thus, loss of HIRA promotes global chromatin condensation and redistribution, thereby regulating the BCR-ABL expression and cell proliferation. Our findings highlight how elevated HIRA expression contributes to the pathogenesis of CML and establish a regulatory axis that could be further explored for therapeutic interventions.