Jumping translocations of chromosome 1q occurring by a multi-stage process in an acute myeloid leukemia progressed from myelodysplastic syndrome with a TET2 mutation

Background: Jumping translocations (JTs) are rare chromosome rearrangements characterized by re-localization of one donor chromosome to multiple recipient chromosomes. Here, we describe an acute myeloid leukemia (AML) that progressed from myelodysplastic syndrome (MDS) in association with acquisition of 1q JTs. The sequence of molecular and cytogenetic changes in our patient may provide a mechanistic model for the generation of JTs in leukemia. Case presentation: A 68-year-old man presented with pancytopenia. Bone marrow aspirate and biopsy showed a hypercellular marrow with multilineage dysplasia, consistent with MDS, with no increase in blasts. Karyotype and MDS fluorescence in situ hybridization (FISH) panel were normal. Repeat bone marrow aspirate and biopsy after 8 cycles of azacitidine, with persistent pancytopenia, showed no changes in morphology, and karyotype was again normal. Myeloid mutation panel showed mutations in RUNX1, SRSF2, ASXL1, and TET2. Three years after diagnosis, he developed AML with myelodysplasia-related changes. Karyotype was abnormal, with unbalanced 1q JTs to the short arms of acrocentric chromosomes 14 and 21, leading to gain of 1q. Conclusions: Our patient had MDS with pathogenic mutations of the RUNX1, SRSF2, ASXL1, and TET2 genes and developed 1q JTs at the time of progression from MDS to AML. Our data suggest that the formation of 1q JTs involves multiple stages and may provide a mechanistic model for the generation of JTs in leukemia.