leukemia Flashcards
what are HSCs, where are they found? (fetus vs adult)
- cells that ultimately give rise to all blood cells
- fetus = yolk sac, then liver & spleen
- adults = found in bone marrow (vertebrae, pelvis and sternum)
give a general overview of hematopoiesis
process by which HSCs give rise to mature blood cells
what are the two defining properties of stem cell (HSC) differentiation?
(1) self-renewal: stem cells can divide while remaining undifferentiated (rare event)
(2) multipotency: stem cells can give rise to multiple cell types by commiting successive differentiation steps
are stem cells mainly in their quiescent or active form?
quiescent
explain the steps of hematopoiesis
(1) HSC makes commitment to myeloid or lymphoid lineage by producing a common myeloid or common lymphoid progenitor
(2) myeloid linage: mature cells in myeloid lineage (e.g. megakaryocytes) produce thrombocytes, eurythrocytes, innate immune cells (neutrophils, eosinophils, machrophages)
(3) lymphoid lineage: cells in the lymphoid lineage contribute to the adaptive immune system (B cells, T cells, Nk cells)
what is the result of pathological stem cell differentiation?
neoplastic cells
define neoplasia
disorder - cell growth that is not under physiological control (uncontrolled)
how is neoplasia acquired?
- through heritable genetic alterations OR
- mutations affecting a single cell and it’s clonal progeny
neoplasms may be benign or malignant, true or false?
true
what are the characteristics of neoplastic cells? (4)
- growth of neoplastic cells exceeds normal surrounding cell growth
- growth of neoplastic cells is autonomous
- autonomous growth is caused by mutations
- all cells in a tumour are direct descendents of a single cell (monoclonal)
define oncogene
cancer-inducing gene responsible for encoding oncoproteins
define proto-oncogene
normal gene that upon mutation acquires the ability to function as an oncogene
define oncoprotein
protein encoded by an oncogene which causes the transformation of a cell into a tumour cell
define tumour suppressor gene
gene whose inactivation contributes to cancer development
deinfe leukemia
cancer affecting the body’s blood forming tissues
what are the two classification of leukemia?
acute and chronic
explain the characteristics of acute leukemia
- proliferation of immature progenitor cells
- progresses rapidly
- immediate treatment usually required
- histology: immature cells with more open nuclear chromatin (less intense stain)
explain the characteristics of chronic leukemia
- proliferation of mature lineage-commited cells
- progresses slowly
- may be monitored before treatment is initiated
- histology: mature cells with more clumped nuclear chromatin (more intense stain)
what are the 4 main types of leukemia
- acute lymphoblastic leukemia (ALL)
- acute myeloid leukemia (AML)
- chronic lymphocytic leukemia (CLL)
- chronic myeloid leukemia (CML)
explain the general pathogenesis of leukemia
- hematopoiesis is dominated by a single clone
- transition towards monoclonal production of blood cells = bc competitive advantage of diseased stem cells
explain the general pathogenesis of AML
- preferential commitment to myeloid linkage
- progeny (blasts) cannot differentiate past the immature myeloid progenitor state
- blasts accumulate
explain the general pathogenesis of ALL
- preferential commitment to lymphoid lineage
- progeny (blasts) cannot differentiate past the immature lymphoid progenitor state
- blasts accumulate
explain the general pathogenesis of CML
maturation primarily occurs towards granulocytes and monocytes
explain the general pathogenesis of CLL
maturation occurs towards predominant B cells
are leukemias often idiopathic or do they have a common cause?
often idiopathic but its known that the etiology is often related to a somatic mutation
list risk factors for leukemia
- history of other blood cancers (increases risk of AML)
- other syndromes that increase genetic predisposition (e.g. certain types of anemia)
- strong family history (most of these = currently unknown)
- genotixic exposures (radiation, chemotherapy, benzene, smoking)
