Chronic Myeloid Leukemia

In our cohort, we observed missense variants clustering in the RHD and recurrence of common pathogenic variants. Higher-risk comutations were found in a substantial fraction of mRUNX1 cases which may contribute to its adverse risk associations. Comparable degrees of aberrancy in B-lineage markers were seen in mRUNX1 patients versus the comparator cohorts of MPAL-wtRUNX1 and AML with rearranged RUNX1.

Tyrosine kinase inhibitors (TKI) are often used in combination with other chemotherapeutic nucleoside/nucleobase analogues, such as gemcitabine and 6-mercaptopurine, in the treatment of various cancers...Gefitinib, which was one of the most effective inhibitors of ENT1, also inhibited ENBT1 with a similar affinity...These data suggest that TKI inhibit multiple purine transporters, likely via interactions with their common purine ring binding domain. However, interactions between TKI and other nucleoside/nucleobase analogue drugs that are substrates for these systems are not likely to be a significant concern at the doses commonly used therapeutically.

EMR should be considered a strong surrogate marker for identifying treatment failure. Imatinib-treated patients achieving EMR and carrying the b3a2 BCR-ABL1 transcript may be suitable for TFR if closely monitored under strict protocols.

Tyrosine kinase inhibitors (TKIs), including imatinib and sunitinib, have revolutionized cancer therapy by selectively targeting kinases such as Bcr-Abl1 (CML) and KIT/PDGFRα (GIST), offering substantial clinical benefits. Compound 4c displayed strong cytotoxic activity against several solid tumor cell lines, including DU145 (3.9 μM), MCF7 (3.5 μM), HT29 (7.7 μM), NCI-H1299 (19.5 μM), and T98G (9.0 μM). Importantly, all tested compounds showed low erythrocytic toxicity (CC₅₀ > 30 μM).

Validated in 70 clinical samples (40 CML patients, 30 healthy volunteers), it distinguished subtypes in bone marrow/peripheral blood, correlated well with qRT-PCR, and evaluated tyrosine kinase inhibitor (TKI) efficacy. This method avoids RNA reverse transcription and multitube reactions, providing a robust tool for CML diagnosis and targeted therapy monitoring.

Dasatinib induced deep molecular remission; however, persistent thrombocytosis required hydroxyurea. This case underscores the importance of vigilance for secondary myeloproliferative neoplasms (MPNs) and clonal evolution when a new hematologic phenotype emerges in a patient with an established MPN. The coexistence of JAK2 V617F and BCR::ABL1 mutations is exceedingly rare and presents significant diagnostic and therapeutic challenges.

The patient achieved complete hematological remission after one cycle of dasatinib combined with hyper-CVAD/MA. Measurable residual disease persisted, and he underwent two cycles of inotuzumab ozogamicin therapy followed by allogeneic hematopoietic stem cell transplantation. This case highlights the critical need for vigilant follow-up in CML patients after prolonged TFR, given the risk of progression to blast crisis.

P=N/A, N=380, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=124, Terminated, Sun Pharma Advanced Research Company Limited | Active, not recruiting --> Terminated; Closed for administrative, non-safety-related reasons.

Integrating cytokine signatures with molecular markers improved prognostic accuracy, supporting immune biomarkers as complements to established clinical parameters. These findings underscore the complexity of relapse mechanisms and the need for individualized risk assessment when considering TKI discontinuation.

P1, N=66, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> May 2028 | Trial primary completion date: Nov 2027 --> May 2028