Loss of H3K36 Methyltransferase SETD2 Impairs V(D)J Recombination during Lymphoid Development.

Repair of DNA double-stranded breaks (DSBs) during lymphocyte development is essential for V(D)J recombination and forms the basis of immunoglobulin variable region diversity. Understanding of this process in lymphogenesis has historically been centered on the study of RAG1/2 recombinases and a set of classical non-homologous end-joining factors. Much less has been reported regarding the role of chromatin modifications on this process.

Inhibition of MEK and ATR is effective in a B-cell acute lymphoblastic leukemia model driven by and activated .

Infant B-cell acute lymphoblastic leukemias (B-ALLs) that harbor rearrangements are associated with a poor prognosis. One important obstacle to progress for this patient population is the lack of immunocompetent models that faithfully recapitulate the short latency and aggressiveness of this disease. Recent whole-genome sequencing of B-ALL samples revealed a high frequency of activating mutations; however, single-agent targeting of downstream effectors of the pathway in these mutated r B-ALLs has demonstrated limited and nondurable antileukemic effects.