Searching leukemia predisposition gene in bone marrow failure syndrome with functional analysis.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: Mitsui Tetsuo 山形大学, 医学部, 教授 (30270846)
• Co-Investigator(Kenkyū-buntansha): 早坂 清 山形大学, 医学部, 名誉教授 (20142961) ; 簡野 美弥子 山形大学, 医学部, 助教 (40400551)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: CSF3受容体 / G-CSF受容体切断型異常 / 骨髄機能不全症候群 / 白血病化

Outline of Final Research Achievements

The genomic instability in patients with bone marrow failure syndrome was observed in a prospective study. An analysis of G-CSF receptor (CSF3R) gene was done in bone marrow failure syndrome, including congenital neutropenia which is a typical disease reported as progressing myelodysplasia and leukemia. Two somatic gene mutations revealed. One was a heterozygous gene mutation (Ala569Val) immediately above the transmembrane portion of the CSF3 receptor, and the other case was a stop codon case of CSF3R731. The first case had no change in her clinical course, and the mutation was disappeared in the six months later in her bone marrow (BM). The second case showed the 8th and 21st chromosome trisomy clones in his BM simultaneously, and allogeneic hematopoietic cell transplantation was performed. These results demonstrate genomic instability in patients with congenital neutropenia. The spontaneous mutation disappearance was also observed in untreated patients.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

こうした一過性のアミノ酸変化や切断型異常の出現は、先天性好中球減少症の患者さんにおけるゲノム不安定性を実証するもので興味深い。また1例目のものは、無治療経過観察の中で、変異は自然に消滅しており、この観察も意義深いと考えられる。他の解析継続症例にはCSF3Rの遺伝子変異は観られずその臨床経過も大きな変化はなく稀少疾患で長期の観察が必要な疾患群であり、数年という短期の検討では、有意な結果を得る事が困難であることが示された。