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Background  Deletions of 6q15–16.1 are recurrently found in pediatric T-cell acute lymphoblastic leukemia (T-ALL). This chromosomal region includes the mitogen-activated protein kinase kinase kinase 7 ( MAP3K7 ) gene which has a crucial role in innate immune signaling and was observed to be functionally and prognostically relevant in different cancer entities. Therefore, we correlated the presence of  MAP3K7  deletions with clinical parameters in a cohort of 327 pediatric T-ALL patients and investigated the function of  MAP3K7  in the T-ALL cell lines CCRF-CEM, Jurkat and MOLT-4.    Methods   MAP3K7  deletions were detected by multiplex ligation-dependent probe amplification (MLPA). T-ALL cell lines were transduced with adeno-associated virus (AAV) vectors expressing anti- MAP3K7  shRNA or a non-silencing shRNA together with a GFP reporter. Transduction efficiency was measured by flow cytometry and depletion efficiency by RT-PCR and Western blots. Induction of apoptosis was measured by flow cytometry after staining with PE-conjugated Annexin V. In order to assess the contribution of NF-κB signaling to the effects of  MAP3K7  depletion, cells were treated with TNF-α and cell lysates analyzed for components of the NF-κB pathway by Western blotting and for expression of the NF-κB target genes  BCL2 ,  CMYC ,  FAS ,  PTEN  and  TNF- α by RT-PCR.    Results   MAP3K7  is deleted in approximately 10% and point-mutated in approximately 1% of children with T-ALL. In 32 of 33 leukemias the deletion of  MAP3K7  also included the adjacent  CASP8AP2  gene.  MAP3K7  deletions were associated with the occurrence of  SIL-TAL1  fusions and a mature immunophenotype, but not with response to treatment and outcome. Depletion of  MAP3K7  expression in T-ALL cell lines by shRNAs slowed down proliferation and induced apoptosis, but neither changed protein levels of components of NF-κB signaling nor NF-κB target gene expression after stimulation with TNF - α.    Conclusions  This study revealed that the recurrent deletion of  MAP3K7/CASP8AP2  is associated with  SIL-TAL1  fusions and a mature immunophenotype, but not with response to treatment and risk of relapse. Homozygous deletions of  MAP3K7  were not observed, and efficient depletion of  MAP3K7  interfered with viability of T-ALL cells, indicating that a residual expression of  MAP3K7  is indispensable for T-lymphoblasts.    Electronic supplementary material  The online version of this article (10.1186/s12885-018-4525-0) contains supplementary material, which is available to authorized users.

MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB