MECOM (MDS1 And EVI1 Complex Locus)

RT-qPCR results showed that NLRP7 and PRDM13 were significantly upregulated in MM group, while GPR15 and CRIM1 were significantly downregulated in MM group (p < 0.05). In this study, 5 MFRGs were identified as prognostic genes (GPR15, NLRP7, ZNF208, PRDM13, and CRIM1) for MM, which provide reference significance for the prognosis of MM.

Current therapeutic approaches-including intensive chemotherapy, hypomethylating agents in combination with venetoclax, and allogeneic stem cell transplantation-are evaluated with particular emphasis on inv(3) and other t(3q26) subtypes. Despite these treatment strategies, outcomes remain poor, underscoring the urgent need for novel, more effective therapies for this high-risk form of AML.

Post-transplant recovery was marked by poor initial engraftment, requiring platelet transfusions and biweekly filgrastim...Despite hematologic recovery, qPCR consistently revealed persistent BCR::ABL1 p190 expression, indicating residual disease. This case underscores the challenge of eradicating leukemic stem cells (LSCs) in high-risk AML and supports the integration of next-generation flow cytometry for enhanced MRD and LSC assessment post-transplant.

However, OGM was effective for detecting enhancer-hijacking events that do not generate fusion transcripts. Both methods are complementary for the workup of acute leukemia cases.

Mutational signature analysis further suggests that defective DNA mismatch repair and homologous recombination may act in concert with SIR-induced DNA structural instability to drive OS development. Our findings highlight SIRs as mutational hotspots and potential drivers of osteosarcoma pathogenesis.

With the advent of targeted therapies, including antibodies such as blinatumomab and inotuzumab and small molecule inhibitors, such as the BCR::ABL1 tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, and venetoclax, the treatment landscape of leukemia has drastically changed, improving survival outcomes while relying less on overall chemotherapy intensity in many leukemia types. Advancements in the treatment of TP53-mutated, MECOM-rearranged, and treated secondary AML are still needed to improve outcomes in these adverse risk groups. The authors also review the recent progress in the treatment of the acute and chronic leukemias.

P2, N=25, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

For instance, mutations in NPM1, FLT3, and DNMT3A, three frequent driver mutations, have high incident rates with differing prognoses and treatments in pediatric and adult patients. AML patients with MECOM face particularly dire outcomes, as well as those with ASXL1 and TP53, making their mutational analysis crucial for review in developing a prognosis.

In addition, AML patients with MECOM overexpression through enhancer hijacking show significantly reduced CEBPA levels. Our study directly connects two major players in normal and malignant hematopoiesis, MECOM and CEBPA, and unveils how MECOM maintains self-renewal by repressing CEBPA-induced differentiation.

After achieving remission with azacitidine and venetoclax, the patient relapsed within ten months, necessitating reevaluation and modification of therapy. The identification of novel abnormalities at relapse may carry prognostic and therapeutic significance and may be used to refine risk stratification. Thus, ongoing cytogenetic monitoring is essential to adapt management approaches in evolving disease contexts.

Importantly, targeted activation of this regulatory element promotes differentiation of these aggressive AMLs and reduces leukemia burden in vivo. These findings suggest a broadly applicable approach for functionally dissecting oncogenic gene regulatory networks to inform improved therapeutic strategies.

On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p < 0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT)...In <20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 &lsqb;95% CI, 0.1-0.8], p < 0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.