Presentation on theme: "MALIGNANCIES OF THE HAEMAPOIETIC STEM CELL. Haemapoietic Stem Cell are pluripotent and give rise to all of the haemopoietic cell under the action of cytokines."— Presentation transcript:
MALIGNANCIES OF THE HAEMAPOIETIC STEM CELL
Haemapoietic Stem Cell are pluripotent and give rise to all of the haemopoietic cell under the action of cytokines. Stem cell are identified by CD34 positivity and CD117 positivity. CD117 is the receptor for stem cell factor
MYELODYSPLASTIC DISORDERS Abnormal looking haemopoitic cells with < 20% blasts in marrow Refractory cytopaenia with unilineage dysplasia Refractory cytopaenias with multilineage dysplasias Refractory anaemia with ringed sideroblasts Refractory anaemia with excess of blasts.
High Risk MDS Refractory Anaemia with Excess of Blasts Secondary MDS from previous chemotherapy Bad cytogenetics : p53 deletion Chr 17p Complex cytogenetics >/= 3 abnormalities
CHRONIC MYELOID LEUKEMIA Chronic phase Accelerated Phase Acute Leukemia within 5 years.
TREATMENT Alkylating agents Interferon-alpha Allogenic bone marrow transplant Tyrosine Kinase inhibitors since 2003 Imatinib (Glivec) Dasatinib and nilotinib
ACUTE LEUKEMIAS Children 70% ALL 30% AML Adults 70% AML 20% ALL 10% Mixed Lineage
AML 1970’s French American British (FAB) Morphology and Cytochemistry Myeloperoxidase (MPO) +ve Myeloblasts Alpha-Napthyl Acetate Esterase +ve for Monoblasts M1 Immature myeloblasts M2 Some mature granulocytes M3 Acute Promyelocytic Leukemia M4 Acute Myelomonocytic Leukemia M5 Acute Monocytic Leukemia M6 Erytholeukemia M7 Megakaryoblastic Leukemia M0 in 1988 : MPO –ve but myeloid marker CD13, CD33 positive by flow cytometry
M0 M1 M2 M3 M4 M5 M6 M7
AML RECURRENT CYTOGENETIC ABNORMALITIES M2 with t(8;21) RUNX1-RUNX1T1 M4 Eos inv 16 (p13.q22) CBFB-MYH11 M3 t(15;17) PML-RARA M4/M5 t(9;11) MLLT3-MLL AML with dysplasia t(6;9) AML with thrombocytosis inv(3)(q21;q26.2) M7 t(1,22)
ACUTE PROMYELOCYTCIC LEUKEMIA Prone to DIC Responds to All-trans retinoic Acid ATRA Responds to low dose Arsenic
ALL RECURRENT CYTOGENETIC ABNORMALITIES B ALL t(9:22) t(12;21) TEL-AML1 or ETV6-RUNX1 t(1;19) t(v;11q23) MLL gene rearranged