Dr. Makishima is a current AA&MDSIF Research grant awardee at Taussig Cancer Institute, Cleveland Clinic, working with Prof. Jaroslaw P. Maciejewski on research related to genetic alterations in bone marrow failure syndromes, including MDS, PNH, and acquired aplastic anemia. Dr. Makishima mentioned that that the differences and diversities of these diseases might come from the variety of genetic change identified in each patient, and he hopes through his work to clarify some of the mutations that contribute to disease presentation and clinical course.
He is the Principal Investigator on a project (Clonal Architecture in PNH: Somatic Genetic Defects Facilitating Clonal Expansion), currently funded by AA&MDSIF Research grant. The goal of this project is to identify novel somatic mutations and cryptic chromosomal aberrations in PNH. As well as PNH, he is investigating novel molecular factors causing other bone marrow failure syndromes. For this purpose, he is using next generation sequencing technology, which is helpful to search genetic abnormality in whole genome of human comprehensively.1 In such a study, Dr. Makishima describes clonal acquisition of genetic lesions in bone marrow failures, including not only PNH but also MDS and aplastic anemia.2 In addition to discovering new mutations of various oncogenes or tumor suppressor genes in MDS, similar findings were provided by his next generation research. He and his colleagues postulate that a common mechanism may be responsible for pathogenesis of MDS and other bone marrow failure. Some questions Dr. Makishima is interested in being able to answer are: Does the genetic abnormalities play a role in PNH and aplastic anemia presentation? Can these diseases be slowed by targeting treatment within associated defective genes? Using both whole genome search and targeted gene survey, Dr. Makishima is studying the most important genetic lesions related to the clinical outcomes of the patients.
Dr. Makishima shared that the opportunity to receive a Research grant from AA&MDSIF has played a critical role in his ability to keep his research going during lean funding times. The financial support he received assisted with his success in progressing towards junior faculty position in order to continue his research.
1. Shen, W. et al. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. J Clin Invest doi:10.1172/JCI74747DS1(2014).
2. Makishima, H. et al. Clinical MUTATOME of myelodysplastic syndrome; comparison to primary acute myelogenous leukemia. Blood (ASH Annual Meeting Abstracts) 122, 518 (2013).