Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21)
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Variant chromosomal translocations associated with t(8;21) are observed in 3–4% of acute myeloid leukemia (AML) cases with a RUNX1–RUNX1T1 fusion gene. However, the molecular events that occur in variants of t(8;21) are not well characterized. In the present study, we report genetic features of a variant three-way translocation of t(8;12;21)(q22;p11;q22) in a patient with AML. In this patient, leukemia cells lacked azurophilic granules, which does not correspond with the classic features of t(8;21). RNA-seq analysis revealed that TM7SF3 at 12p11 was fused to VPS13B at 8q22 and VPS13B to RUNX1, in addition to RUNX1–RUNX1T1. VPS13B was located near RUNX1T1 and both were localized at the same chromosomal bands. The reading frames of TM7SF3 and VPS13B did not match to those of VPS13B and RUNX1, respectively. Disruption of VPS13B causes Cohen syndrome, which presents intermittent neutropenia with a left-shifted granulopoiesis in the bone marrow. Disruption of VPS13B may thus cause the unusual features of RUNX1–RUNX1T1 leukemia. Our case indicates that rearrangement of VPS13B may be additional genetic events in variant t(8;21).
KeywordsAML RUNX1–RUNX1T1 VPS13B TM7SF3 3-Way translocation
This work was supported by JSPS KAKENHI Grant Number 16K09860 to AA, a Grant-in-Aid from Fujita Health University to NE and the MEXT-Supported Program for the Strategic Research Foundation at Private Universities from the Ministry of Education, Culture, Sports, Science and Technology (MEXT). We sincerely thank Sachiko Iba for valuable laboratory assistance. We greatly appreciate Dr. Yuya Ouchi, Dr. Hidehito Inagaki, and Dr Hiroki Kurahashi (Genome and Transcriptome Analysis Center, FHU) for technical assistance of next-generation sequencing.
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Conflict of interest
The authors declare no conflict of interest.
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