leukemia

Question 1

what are HSCs, where are they found? (fetus vs adult)

Answer 1

• cells that ultimately give rise to all blood cells
• fetus = yolk sac, then liver & spleen
• adults = found in bone marrow (vertebrae, pelvis and sternum)

Question 2

give a general overview of hematopoiesis

Answer 2

process by which HSCs give rise to mature blood cells

Question 3

what are the two defining properties of stem cell (HSC) differentiation?

Answer 3

(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

Question 4

are stem cells mainly in their quiescent or active form?

Answer 4

quiescent

Question 5

explain the steps of hematopoiesis

Answer 5

(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)

Question 6

what is the result of pathological stem cell differentiation?

Answer 6

neoplastic cells

Question 7

define neoplasia

Answer 7

disorder - cell growth that is not under physiological control (uncontrolled)

Question 8

how is neoplasia acquired?

Answer 8

• through heritable genetic alterations OR

- mutations affecting a single cell and it’s clonal progeny

Question 9

neoplasms may be benign or malignant, true or false?

Answer 9

true

Question 10

what are the characteristics of neoplastic cells? (4)

Answer 10

• 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)

Question 11

define oncogene

Answer 11

cancer-inducing gene responsible for encoding oncoproteins

Question 12

define proto-oncogene

Answer 12

normal gene that upon mutation acquires the ability to function as an oncogene

Question 13

define oncoprotein

Answer 13

protein encoded by an oncogene which causes the transformation of a cell into a tumour cell

Question 14

define tumour suppressor gene

Answer 14

gene whose inactivation contributes to cancer development

Question 15

deinfe leukemia

Answer 15

cancer affecting the body’s blood forming tissues

Question 16

what are the two classification of leukemia?

Answer 16

acute and chronic

Question 17

explain the characteristics of acute leukemia

Answer 17

• proliferation of immature progenitor cells
• progresses rapidly
• immediate treatment usually required
• histology: immature cells with more open nuclear chromatin (less intense stain)

Question 18

explain the characteristics of chronic leukemia

Answer 18

• 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)

Question 19

what are the 4 main types of leukemia

Answer 19

• acute lymphoblastic leukemia (ALL)
• acute myeloid leukemia (AML)
• chronic lymphocytic leukemia (CLL)
• chronic myeloid leukemia (CML)

Question 20

explain the general pathogenesis of leukemia

Answer 20

• hematopoiesis is dominated by a single clone

- transition towards monoclonal production of blood cells = bc competitive advantage of diseased stem cells

Question 21

explain the general pathogenesis of AML

Answer 21

• preferential commitment to myeloid linkage
• progeny (blasts) cannot differentiate past the immature myeloid progenitor state
• blasts accumulate

Question 22

explain the general pathogenesis of ALL

Answer 22

• preferential commitment to lymphoid lineage
• progeny (blasts) cannot differentiate past the immature lymphoid progenitor state
• blasts accumulate

Question 23

explain the general pathogenesis of CML

Answer 23

maturation primarily occurs towards granulocytes and monocytes

Question 24

explain the general pathogenesis of CLL

Answer 24

maturation occurs towards predominant B cells

Question 25

are leukemias often idiopathic or do they have a common cause?

Answer 25

often idiopathic but its known that the etiology is often related to a somatic mutation

Question 26

list risk factors for leukemia

Answer 26

- 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)