Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21)

• Published in: International journal of hematology Vol. 108; no. 2; pp. 208 - 212
• Main Authors: Abe, Akihiro, Yamamoto, Yukiya, Katsumi, Akira, Okamoto, Akinao, Tokuda, Masutaka, Inaguma, Yoko, Yamamoto, Kiyoko, Yanada, Masamitsu, Kanie, Tadaharu, Tomita, Akihiro, Akatsuka, Yoshiki, Okamoto, Masataka, Kameyama, Toshiki, Mayeda, Akila, Emi, Nobuhiko
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-08-2018; Springer Nature B.V
• Subjects: Acute myeloid leukemia; Bone marrow; Case Report; Chromosome translocations; Cohen syndrome; Fusion protein; Gene rearrangement; Granule cells; Granulopoiesis; Hematology; Leukemia; Medicine; Medicine & Public Health; Myeloid leukemia; Neutropenia; Oncology; Ribonucleic acid; RNA; Runx1 protein; Translocation; AML; 3-Way translocation; RUNX1–RUNX1T1; VPS13B; TM7SF3
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-017-2387-x

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).