Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome

Hironori Arai
,
Hirotaka Matsui
ORCID logo ,
SungGi Chi
ORCID logo ,
Yoshikazu Utsu
,
Shinichi Masuda
,
Nobuyuki Aotsuka
,
Yosuke Minami
* ORCID logo
Version 1 : Received: 7 November 2023 / Approved: 7 November 2023 / Online: 8 November 2023 (01:43:02 CET)

A peer-reviewed article of this Preprint also exists.

Arai, H.; Matsui, H.; Chi, S.; Utsu, Y.; Masuda, S.; Aotsuka, N.; Minami, Y. Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome. Int. J. Mol. Sci. 2024, 25, 652. Arai, H.; Matsui, H.; Chi, S.; Utsu, Y.; Masuda, S.; Aotsuka, N.; Minami, Y. Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome. Int. J. Mol. Sci. 2024, 25, 652.

Abstract

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.

Keywords

HHMS; AML; MDS; DDX41; TP53; SAMD9; SAMD9L; germline; variant

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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