Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Normal Hematopoiesis

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Normal Hematopoiesis: Pluripotent and Multipotent Stem Cells

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Normal Hematopoiesis: Amplification of Committed Progenitor Cells

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Normal Hematopoiesis: Factors that Influence Hematopoietic Cell Proliferation, Differentiation and Survival

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Abnormal Hematopoiesis: Cytopenia

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Abnormal Hematopoiesis: Later MDS and Abnormal Blood Cell Morphology

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Abnormal Hematopoiesis: Early MDS

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Abnormal Hematopoiesis: Abnormal Cytogenetics

Myelodysplastic Syndromes, Introduction to Myelodysplastic Syndromes, Interactive Exercise: Cancer Vocabulary

Myelodysplastic Syndromes (MDS)

• A diverse group of neoplastic bone marrow disorders
• Deficiencies in one or more types of blood cells
• Risk for progression to Acute Myeloid Leukemia (AML)

Normal Hematopoiesis

• Types of Blood Cells
  • Red blood cells: Erythrocytes
    • Oxygen Transport
  • White blood cells: Leukocytes
    • Fight Infection
  • Platelets: Thrombocytes
    • Blood Coagulation

Pluripotent and Multipotent Stem Cells

• Pluripotent: Able to generate numerous cell types.
• Multipotent: Able to generate a limited number of cell types.

Normal Hematopoiesis

• Amplification of Committed Progenitor Cells

Terminally differentiated: Specialized cells that are unable to proliferate.

Normal Hematopoiesis

Factors that Influence Hematopoietic Cell Proliferation, Differentiation and Survival

• Growth Factor: Stem Cell Factor (SCF)
• Colony Stimulating Factor(CSF): Erythropoietin (EPO)

Abnormal Hematopoiesis

• Cytopenia: Decreased mature, circulating blood cells
  • Red Blood Cells: Anemia
  • White Blood Cells: Neutropenia
  • Platelets: Thrombocytopenia

Abnormal Hematopoiesis- Later MDS

• Increased Proliferation
• Loss of Differentiation
• Decreased Apoptosis

Abnormal Blood Cell Morphology

• Normal Erythroblast
• Ringed Sideroblast
• Auer Rods
• Morphology: The form and structure of a cell

Increased Apoptosis (Programmed Cell Death):

• Occurs as a normal part of the development of an organism and its tissues
• Caused by changes in the bone marrow microenvironment that lead to an overproduction of factors such as tumor necrosis factor alpha

Abnormal Cytogenetics - Trigger for Abnormal Hematopoiesis

• Epigenetic: Heritable changes in DNA that do not result in changes in DNA sequence
• Cytogenetic: Heritable changes in chromosomes or genes within chromosomes

Myelodysplastic syndromes are a heterogeneous group of acquired bone marrow disorders of altered hematopoiesis resulting in peripheral cytopenias.  

Hematopoiesis: The formation and development of blood cells in the bone marrow

Cytopenias: A reduction in the number of cells in the blood

Transformation: The change that a normal cell undergoes as it becomes malignant

Acute Leukemia: A rapidly progressing cancer of the blood-forming tissue in the bone marrow

Dysplasia: Abnormal cell growth

Morphology: The form or structure of a cell or organ

Apoptosis: Programmed cell death

Proliferation: An increase in the number of cells as a result of cell growth and cell division

Epigenetic: Heritable changes in DNA that do not result in changes in DNA sequence

Cytogenetic: Heritable changes in chromosomes or genes within chromosomes

D.P. Steensma and J.M. Bennett. The Myelodyplastic Syndromes: Diagnosis and Treatment. Mayo Clin Proc. 2006.

B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter. Molecular Biology of the Cell. 4th Edition. Garland Science of the Taylor & Francis Group. New York, N.Y., 2002.

D.V.T. Catenacci and G.J. Schilller. Meyelodyplastic Syndromes: A Comprehensive Review. Blood Reviews. 2005.

H.T. Nishino, C.-C. Chang. Myeolodysplastic Syndromes. Clinicopathologic Features, Pathobiology, and Molecular Pathogenesis. Arch Pathol Lab Med. 2005.

G. Yue, S. Hao, O. Fadare, S. Baker, O. Pozdnyakova, N. Galili, B.A. Woda, A. Raza, S.A. Wang. Hypocellularity in Myelodysplastic Syndrome is an Independent Factor Which Predicts a Favorable Outcome. Leukemia Research. 2008.

D. Marisavljevic, V. Cemerikic, Z. Rolovic, D. Boskovic, M. Colovic. Hypocellular Myelodysplastic Syndromes. Clinical and Biological Significance. Medical Oncology. 2005.

P.L. Greenberg, N.S. Young and N. Gatterman. Myelodysplastic Syndromes. Hematology Am Soc Hematol Educ Program. 2002.

Neoplastic: Associated with abnormal cell growth.

Hematopoiesis: The development of blood cells.

Multipotent Progenitor: A precursor cell with the ability to differentiate into other cells.

Anemia: Decreased number of circulating red blood cells.

AML = Acute Myeloid Leukemia

MDS = Myelodysplastic Syndromes

Red blood cells: Erythrocytes

White blood cells:  Leukocytes

Platelets:  Thrombocytes

Pluripotent: Able to generate numerous cell types.

Multipotent: Able to generate a limited number of cell types.

Terminally differentiated: Specialized cells that are unable to proliferate.

SCF = Stem Cell Factor

CSF = Colony Stimulating Factor

EPO = Erythropoietin 

Anemia: Decreased number of ciruclating red blood cells.

Neutropenia: Decreased number of circulating neutrophils (white blood cells).

Thrombocytopenia: Decreased number of circulating platelets.

Morphology: The form and structure of a cell

TNFα = Tumor Necrosis Factor Alpha

Epigenetic: Heritable changes in DNA that do not result in changes in DNA sequence

Cytogenetic: Heritable changes in chromosomes or genes within chromosomes.