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Heme/Onc by Minnie (she/her) > 246 - Stem Cells and Hematopoiesis > Flashcards

246 - Stem Cells and Hematopoiesis Flashcards

1
Q

Where is thrombopoietin produce?

A

Liver

Liver failure -> no thrombopoietin -> no platelets :(

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2
Q

What causes myelodysplastic syndrome?

A

Accumulation of mutations in the hematopoetic stem cell genome

May be a combo of toxic chemicals, radiation, predisposition due to genetic abnormality

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3
Q

What is the treatment for Fanconi Anemia?

A

Stem cell transplant

  • Ideally, do before leukemia develops
    • AML likely to develop in adolescence w/o transplant
  • Head, neck, and/or lung cancer likely to develop later, even after successful stem cell transplant
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4
Q

List 4 cytokines involved in myelopoiesis

A
  • IL-3
    • ​Prevents CMP apoptosis
  • GM-CSF (granulocyte/monocyte colony stimulating factor)
    • CMP -> GMP
  • G-CSF (granulocyte colony stimulating factor)
    • GMP -> PMN
  • M-CSF (monocyte colony stimulating factor)
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5
Q

Hematopoietic stem cells first differentiate into either common lymphoid progenitor cells or common myeloid progenitor cells

What kinds of cells will each of these lines eventually become?

A
  • Common lymphoid
    • T cells
    • B cells
    • Differentiation occurs outside of the bone marrow niche
  • Common myeloid
    • Megakaryocyte erythroid progenitors -> RBCs and platelets
    • Granulocyte monocyte progenitors -> Granulocytes, monocytes, eosinophils, basophils
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6
Q

List 2 treatments for myelodysplastic syndrome

A
  • Stem cell transplantation
    • In younger patients
  • Nucleoside analogues (5-azacytidine)
    • Does not help if MDS has progressed to AML

MDS results from accumulation of mutations in the hematopoetic stem cell genome

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7
Q

Which gene is mutated in Schwachman-Diamond syndrome?

List 3 manifestations of the syndrome

A

SDBS gene

Function unknown, but results in these manifestations in childhood:

  • Bone marrow failure
  • Exocrine pancreas failure (diabetes)
  • Growth delay
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8
Q

Is erythropoietin useful in the treatment of pernicious anemia?

A

No

  • Definitely useful in renal insufficiency or after chemotherapy*
  • Maybe useful in myelodysplastic syndrome or early aplastic anemia*
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9
Q

The mutation that causes Fanconi Anemia results in impairment of what cellular process?

A

Cross-link repair

  • Cross-link repair is especially important during a stress response, in tissues where cell proliferation is upregulated
  • 20+ proteins are involved, many different mutations possible
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10
Q

What is the major growth factor that stimulates thrombopoiesis?

What is its effect? (receptor level)

A

Thrombopoietin

  • Interacts with c-mpl receptor on megakaryocyte erythroid precursor (MEP) cells
    • -> differentiation of MEP to megakaryocyte -> platelet

Basically, increases platelet production

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11
Q

List 2 clinical scenarios in which hematopoietic cytokines are used therapeutically

Which cytokines are used?

A
  • Renal failure
    • EPO is usually produced by renal parenchyma
    • Supplement to treat anemia in renal failure
  • After chemotherapy
    • Use G-CSF to decrease severity of infections and need for transfusion
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12
Q

Which cells are produced in the process of myelopoiesis? (4)

A

Granulocytes, monocytes (innate immune system)

Also Basophils, eosinophils

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13
Q

List 3 congenital disorders associated with hematopoietic stem cell dysfunction

A
  • Fanconi Anemia
    • Ineffective cross-link repair
  • Dyskeratosis Congenita
    • Telomerase dysfunction -> shortened telomeres
  • Schwachman-Diamnond Syndrome
    • ​Mutation in SDBS gene
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14
Q

How do the instructive and stochastic models of hematopoietic stem cell homeostasis differ?

A

Both models attempt to explain how hematopoietic stem cells (HCS) decide whether to differentiate or proliferate

  • Instructive
    • Growth cell stimulation influences HCS activity (ex: Erythropoietin)
    • May make the most sense when the body is responding to stress
  • Stochastic
    • Local factors in the niche influence HCS activity
    • May make the most sense during steady state
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15
Q

List the 2 major causes of aplastic anemia

A
  • Autoimmune: T-cell mediated
  • Acute damage due to drugs or radiation
    • Ex: Cloramphenicol
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16
Q

How can you differentiate between myelodysplastic syndreome (MDS) and aplastic anemia?

A

Bone marrow biopsy

  • MDS will have abnormal biopsy
    • Results from chromosomal gains/losses in the hematopoietic stem cell pool
  • Aplastic Anemia will have normal bone marrow biopsy at first
    • Will eventually evolve to “empty bone marrow
17
Q

The mutation that causes Dyskeratosis Congenita results in impairment of what cellular process?

A

Telomerase dysfunction -> shortened telomeres

  • Results in symptoms similar to normal aging
    • Bone marrow failure
    • Skin/nail abnormalieties
    • Leukoplakia -> head and neck cancer

Tx = stem cell transplant before bone marrow failure

18
Q

In myelopoesis, which cytokine promotes differentiation the granulocyte myloid progenitor (GMP) to a polymorphonuclear cell (PMN)?

A

G-CSF

Granulocyte colony stimulating factor

19
Q

What skeletal abnormality is most common in Fanconi Anemia?

A

Malformation of thumbs

20
Q

List the 2 relevant types of cytokine receptors

How do they differ?

A
  • Class I cytokine receptors
    • No endogenous kinase activity
    • Act as docking sites for proteins that are kinases
    • May for heterodimers (beta-common chain) or homodimers (hematopoietin)
  • Class III cytokine receptor
    • Endogenous kinase activity - tyrosine kinase receptor
    • Ex: VEGF-R-like receptors
21
Q

What is the major growth factor that stimulates erythropoiesis?

What is its effect (on a receptor level)

A

Erythropoietin

  • Interacts with its receptor on Megakaryocyte erythrocyte progenitor (MEP) cells
    • -> Differentiaon to RBC

Basically, promotes production of RBCs

Clinically useful in the tx of renal insufficiency and after chemotherapy

22
Q

What is the most serious possible consequence of a hematopoietic stem cell transplant in a patient with Fanconi Anemia?

A

Head, neck, or lung cancer later in life

Hematopoietic stem cell transplant will help with anemia, but mutation in Fanconi Anemia is present in all cells - head, neck, lung cells undergo high turnover, susceptible to cancer

23
Q

In myelopoesis, which cytokine promotes differentiation of the common myeloid progenitor (CMP) to a granulocyte myloid progenitor (GMP)?

A

GM-CSF

Granulocyte-monocyte colony stimulating factor

24
Q

In myelopoesis, which cytokine prevents apoptosis of the common myelpoid progenitor (CMP) cell?

A

IL-3

Heme/Onc by Minnie (she/her) (36 decks)

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