The role of SALL4 in myelodysplastic syndrome

Research Project

Project/Area Number	17K09930
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Hematology
Research Institution	Kumamoto University
Principal Investigator	Tatetsu Hiro 熊本大学, 病院, 講師 (00433029)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	骨髄異形成症候群 / SALL4 / MDS
Outline of Final Research Achievements	Myelodysplastic syndrome (MDS) is a group of heterogeneous diseases characterized by cytologic dysplasia and refractory cytopenias as a result of ineffective　hematopoiesis.　　　Some MDS cases progress to acute myeloid leukemia (AML) with poor prognosis and short survival time. We have reported that oncofetal protein SALL4 can be used as a prognostic biomarker in MDS disease.In this study, we evaluated the expression of SALL4 using single-cell mass cytometry (CyTOF) and Nanostring nCounter. SALL4 was expressed in various MDS BM cells. P53, which is an adverse prognostic marker, positive cells were chiefly seen in SALL4 positive CD34+ cells, erythroid cells and part of myeloid cells. These results indicated that SALL4 could be a candidate of target for MDS therapy.
Academic Significance and Societal Importance of the Research Achievements	骨髄異形成症候群（MDS）は、未だ難治性血液疾患であり、治療法の開発が急務な疾患です、今回、私達は、さまざまな腫瘍に高発現を認めるSALL4に着目し、マスサイトメトリーやナノストリングの手法を用いて解析を行ないました。正常骨髄と比べ、MDS骨髄においては、造血幹細胞を含むさまざな細胞でタンパクレベルでのSALL4の高発現を認めました。また、SALL4の高発現細胞の一部は、予後不良因子であるP53も高発現していました。SALL4陽性細胞は、治療のターゲットとなる可能性が示唆され、今後、SALL4の機能解析をさらに進めるとともにSALL4をターゲットとした治療法の開発を進めたいと考えました。