Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies.

The gene that encodes de novo DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia genomes. Point mutations at position R882 have been shown to cause a dominant negative loss of DNMT3A methylation activity, but 15% of DNMT3A mutations are predicted to produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with WT DNMT3A, strongly supporting the haploinsufficiency hypothesis.

Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia.

The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse.

Diagnosis and expedited surgical intervention of a complete hamstring avulsion in a military combatives athlete: a case report.

Background And Purpose: Hamstring injuries are frequent injuries in athletes, with the most common being strains at the musculotendinous junction or within the muscle belly. Conversely, hamstring avulsions are rare and often misdiagnosed leading to delay in appropriate surgical interventions. The purpose of this case report is to describe the history and physical examination findings that led to appropriate diagnostic imaging and the subsequent diagnosis and expedited surgical intervention of a complete avulsion of the hamstring muscle group from the ischium in a military combatives athlete.