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 bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndromes, including MDS, PNH, and acquired aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… . 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 bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the 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 anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. 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 mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. acquisition in paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… . J Clin Invest doi:10.1172/JCI74747DS1(2014).
2. Makishima, H. et al. Clinical MUTATOME of myelodysplastic syndrome; comparison to primary acute myelogenous leukemia acute myelogenous leukemia: (uh-KYOOT my-uh-LAH-juh-nuss loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of… . Blood (ASH Annual Meeting Abstracts) 122, 518 (2013).