E Pluribus Unum Bone Marrow Jack Goldberg MD Clinical Professor of Medicine University of Pennsylvania Origins of Leukemia Lymphopoiesis Monocytopoiesis stem Pluripotent stem cell Granulopoiesis Sites of Hematopoiesis (Hemocytoblast) cell Erythropoiesis Thrombopoiesis • Yolk sac Pro-erythroblast • Liver and spleen Lymphoblast Monoblast Myeloblast Megakaryoblast Basophilic Pro-Myelocyte erythroblast • Bone marrow – Gradual replacement of Myelocyte Polychromatic erythroblast active (red) marrow by tissue inactive (fatty) Orthocromatic Metamylelocyte erythroblast – Expansion can occur during increased need for Band granulocyte Reticulocyte Megakaryocyte cell production Lymphocyte RBC Platelets Monocyte Granulocyte BLOOD IS MADE IN THE BONE MARROW • Axial skeleton • Inner spongy bone • Bone marrow is in the holes • Bone marrow is a highly organized / regulated organ DMM00_B3.ppt 1 BONE MARROW: THE SOURCE OF BLOOD AND OUR Introduction IMMUNE SYSTEM • All blood cells arise from • Limited Life span of : “mother” (stem) cells – Self renewing • Granulocytes – Safe from harm • Erythrocytes – Pluripotent • Platelets • Blood production is highly regulated • Lymphocytes – Messages from the body (e.g. erythropoietin from kidney) – Microenvironments produce specific cells Normal bone • Cytokines (SCF, IL3) marrow • Growth factors (G-CSF) BAS03_20.ppt Regulation of Haemopoiesis Introduction • Stem cells • Self renewal • Plasticity Controlled cell Controlled cell production • Progenitor cells death • Developmentally-restricted cells • Mature cells • There should be a balance between cell production • Mature cell production takes place from the more developmentally-restricted progenitors and cell death except at the times of requirement Regulation of Haemopoiesis Interaction of stromal cells, growth factors and haemopoietic cells Local environmental control Stromal cell mediated Haemopoiesis Haemopoietic Apoptosis growth factors (Humoral regulation) 2 Lymphoid T Lymphocyte Local and Humoral regulation of Progenitor Cell LPC Haemopoiesis B Lymphocyte Megakaryocyte CFU-Meg Committed PSC CSC Platelets Stem Cell Pluripotent BFU- Stem Cell CFU- RBC E E Colony-forming Myeloid Unit - Erythroid MPC Progenitor CFU- Monocyte Cell M Colony-forming Unit -Monocyte CFU- CFU- G Neutrophil GM Colony-forming Unit - Monocyte.Granulocyte CFU- Eosinophil Eo HEMATOPOIESIS CFU- Basophil Early lineages Mast Lymphoid T Lymphocyte Progenitor Cell LPC B Megakaryocyte Lymphocyte CFU-Meg Committed TPO PSC CSC Platelets Stem Cell Pluripotent SCF BFU- EPO Stem Cell CFU- RBC IL-1 E E Myeloid * MPC Progenitor CFU- M-CSF Monocyte Cell * M IL-3, CFU- GM-CSF * G-CSF Neutrophil * CFU- G GM Colony-forming Unit - Monocyte.Granulocyte * CFU- Eosinophil Eo IL-6 HEMATOPOIESIS CFU- IL-3 Basophil Growth factors Mast 3.