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

Akihiro Abe, Yukiya Yamamoto, Akira Katsumi, Akinao Okamoto, Masutaka Tokuda, Yoko Inaguma, Kiyoko Yamamoto, Masamitsu Yanada, Tadaharu Kanie, Akihiro Tomita, Yoshiki Akatsuka, Masataka Okamoto, Toshiki Kameyama, Akira Maeda, Nobuhiko Emi

Research output: Contribution to journalArticle

Abstract

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).

Original languageEnglish
Pages (from-to)208-212
Number of pages5
JournalInternational Journal of Hematology
Volume108
Issue number2
DOIs
Publication statusPublished - 01-08-2018

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Acute Myeloid Leukemia
Leukemia
Reading Frames
Genetic Translocation
Gene Fusion
Neutropenia
Genes
Bone Marrow
RNA
Cohen syndrome

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

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 ; Maeda, Akira ; Emi, Nobuhiko. / Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21). In: International Journal of Hematology. 2018 ; Vol. 108, No. 2. pp. 208-212.
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abstract = "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).",
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Abe, A, Yamamoto, Y, Katsumi, A, Okamoto, A, Tokuda, M, Inaguma, Y, Yamamoto, K, Yanada, M, Kanie, T, Tomita, A, Akatsuka, Y, Okamoto, M, Kameyama, T, Maeda, A & Emi, N 2018, 'Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21)', International Journal of Hematology, vol. 108, no. 2, pp. 208-212. https://doi.org/10.1007/s12185-017-2387-x

Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21). / 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; Maeda, Akira; Emi, Nobuhiko.

In: International Journal of Hematology, Vol. 108, No. 2, 01.08.2018, p. 208-212.

Research output: Contribution to journalArticle

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T1 - Rearrangement of VPS13B, a causative gene of Cohen syndrome, in a case of RUNX1–RUNX1T1 leukemia with t(8;12;21)

AU - Abe, Akihiro

AU - Yamamoto, Yukiya

AU - Katsumi, Akira

AU - Okamoto, Akinao

AU - Tokuda, Masutaka

AU - Inaguma, Yoko

AU - Yamamoto, Kiyoko

AU - Yanada, Masamitsu

AU - Kanie, Tadaharu

AU - Tomita, Akihiro

AU - Akatsuka, Yoshiki

AU - Okamoto, Masataka

AU - Kameyama, Toshiki

AU - Maeda, Akira

AU - Emi, Nobuhiko

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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).

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