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Heme / Onc > SM_246b: Stem Cells and Hematopoiesis > Flashcards

SM_246b: Stem Cells and Hematopoiesis Flashcards

1
Q

Hematopoiesis is ____

A

Hematopoiesis is the process for hematopoietic stem cells to become mature blood cells

  • Sequential acquisition of lineage specific characteristics
  • Results in production of all blood cell types
  • Continuous process through the life of the organism
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2
Q

Hematopoietic stem cells are ____, ____, and have ____

A

Hematopoietic stem cells are pluripotent, self-renewing, and having homing capability

  • Pluripotent: ability to differentiate into any of the mature blood cells
  • Self-renewing: able to proliferate and create daughter cells to maintain hematopoietic stem cell pool
  • Homing capability: occassionally transit circulation but able to identify bone marrow “niche”
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3
Q

Regulation of hematopoietic stem cells involves a choice between ____ and ____

A

Regulation of hematopoietic stem cells involves a choice between differentiation and proliferation

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4
Q

Hematopoietic stem cell depletion results in ____

A

Hematopoietic stem cell depletion results in bone marrow failure

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5
Q

Hematopoietic stem cell maintenance results in ____

A

Hematopoietic stem cell maintenance results in steady state production

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6
Q

Hematopoietic stem cell expansion results in ____

A

Hematopoietic stem cell expansion results in stress production

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7
Q

Embryonic stem cells are derived from ____ and then ____

A

Embryonic stem cells are derived from blastocyst inner cell mass and then cultured under growth factor conditions to generate specific cell types (such as hematopoietic tissues)

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8
Q

Definitive hematopoiesis occurs in ___

A

Definitive hematopoiesis occurs in bone marrow in adult

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9
Q

Pluripotent hematopoietic stem cells differentiate into ____ or ____

A

Pluripotent hematopoietic stem cells differentiate into common lymphoid progenitors or common myeloid progenitors

  • Common lymphoid progenitors: B cells and T cells, development outside of bone marrow niche
  • Common myeloid progenitors: megakaryocyte erythroid progenitors (RBCs and platelets), granulocyte monocyte progenitors (granulocytes / monocytes / basophils / eosinophils)
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10
Q

Hematopoietic stem cell differentiation results in ____ and ____

A

Hematopoietic stem cell differentiation results in loss of pluripotency (irreversible commitment) and loss of self-renewal (mitotic arrest in mature cells)

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11
Q

Describe changes that occur in erythropoiesis

A

Erythropoiesis

  • Cytoplasm changes from blue to orange: decrease in RNA, increase in hemoglobin
  • Nucleus becomes smaller
  • Chromatin pattern becomes more aggregated
  • Production time: 5 days
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12
Q

___ is the major growth factor for RBC development

A

Erythropoietin is the major growth factor for RBC development

  • Produced by kidney in response to changes in blood O2 tension, decrease in renal failure resulting in anemia
  • Function: interacts with Epo-R on megakaryocyte-erythryoid progenitor, stimulates proliferation on megakaryocyte-erythryoid progenitor, and induces differentiation of on megakaryocyte-erythryoid progenitor to RBC
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13
Q

Describe thrombopoietin

A

Thrombopoietin

  • Produced by hepatocytes
  • Functions: interacts with c-mpl receptor on megakaryocyte-erythryoid progenitor, induces differentiation of megakaryocyte-erythroid progenitor to megakaryocyte, increases platelet production (late differentiation)
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14
Q

Myelopoiesis is ___

A

Myelopoiesis is granulocyte and monocyte development

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15
Q

Granulopoiesis takes ___

A

Granulopoiesis takes 5-7 days

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16
Q

Describe cytokines involved in granulocyte and monocyte differentiation

A

Cytokines involved in granulocyte and monocyte differentiation

  • IL-3
  • GM-CSF
  • G-CSF
  • M-CSF
17
Q

Describe IL-3

A

IL-3

  • Produced by T cells
  • Functions: interacts with IL-3-R, prevents apoptosis in CMP, does not induce differentiation
  • Not useful clinically
18
Q

Describe GM-CSF

A

GM-CSF

  • Produced by T cells, endothelial cells, and fibroblasts
  • Functions: interacts with GM-CSF-R, stimulates differentiation of CMP to GMP, antagonizes apoptosis and increases proliferation in GMP, primes granulocytes for activation
  • Clinical use: shortens post-chemo neutropenia, has side effects
19
Q

Describe G-CSF

A

G-CSF

  • Produced by T-cells, endothelial cells, and fibroblasts
  • Functions: interactions with G-CSF-R on GMP, stimulates differentiation of GMP to PMH, and initially increases proliferation of GMP
  • Clinical uses: shortens neutropenia post chemo, increases granulocytes in patients with severe congenital neutropenia
20
Q

Describe cytokine regulation of hematopoiesis

A

Cytokine regulation of hematopoiesis

  • Hematopoietic cytokines (growth factors): complex networks, different combinations have different results
  • Some common usage between lineage: earlier in differentiation, more specific cytokines required as each lineage differentiates
21
Q

Describe cytokine receptors involved in hematopoiesis

A

Cytokine receptors involved in hematopoiesis

  • Three domains: extracellular, transmembrane, intercellular
  • Ligand binding: activation of signaling cascades
  • Class I cytokine receptors: no endogenous kinase activity
  • Class III cytokine receptors: tyrosine kinase domains
22
Q

Describe class I cytokine receptors

A

Class I cytokine receptors

  • Extracellular domain: ligand binding causes dimerization, induces conformational change
  • Intercellular domain: Src homology domains are binding site for signaling proteins, positive regulatory domains increase proliferation / survival / differentiation, negative regulatory domains are off signals
23
Q

Beta common chain receptors are ____ and form ____

A

Beta common chain receptors are class I cytokine receptors and form heterodimers

  • Same beta chain, different alpha chain
  • Examples: IL3-R, IL5-R, GM-CSF-R
24
Q

Hematopoietin is a ____ that forms ____

A

Hematopoietin is a class I cytokine receptor that forms homodimers that are specific for ligand interaction

  • Examples: Epo-R, G-CSF-R
25
Q

Describe class III cytokine receptors

A

Class III cytokine receptors

  • Extracelliular domain: ligand binding causes dimerization, induces conformational change
  • Intercellular domain: juxtamembrane domain activates signaling, kinase domains phosphorylate intermediates and activate signaling cascades
  • VEGF-R like relevant to hematopoiesis: Flt3, PDFR-R, M-CSF, Kit, FGF
26
Q

Fanconi anemia results from a ___ defect

A

Fanconi anemia results from a DNA repair defect

  • Ineffective cross-link repair
27
Q

Fanconi anemia presents as ____, ____, and ____

A

Fanconi anemia presents as

  • Bone marrow failiure at an early age
  • Acute myeloid leukemia in adolescence
  • Variable skeletal abnormalities
28
Q

Dyskeratosis congenita results from a ___ defect

A

Dyskeratosis congenita results from a telomere defect

  • Shortened telomeres due to telomerase dysfunction
  • Similar changes seen with normal with aging
29
Q

Dyskeratosis congenita presents in ____ with ____, ____, and ____

A

Dyskeratosis congenita presents in childhood with bone marrow failure, abnormalitiies of skin and nails, and leukoplakia progressing to head / neck cancers

30
Q

Shwachman-Diamond syndrome results from ___

A

Shwachman-Diamond syndrome results from a mutation in the SDBS gene

  • Function unknown but may influence ribosome function
31
Q

Shwachman-Diamond syndrome presents in ____ with ____, ____, and ____

A

Shwachman-Diamond syndrome presents in childhood with bone marrow failure, exocrine pancreas failure, and growth delay

32
Q

Myelodysplastic syndrome results from ____

A

Myelodysplastic syndrome results from an accumulation of mutations in the hematopoietic stem cell genome

  • Often history of remote toxic chemical / radiation exposure
  • Undefined inherited genetic abnormalities
33
Q

Myelodysplastic syndrome presents in ____ with ____, ____, and ____

A

Myelodysplastic syndrome presents in older adults with bone marrow failure / pancytopenia that evolves over time, accumulation of chromosomal gains / losses, and evolution to acute myeloid leukemia

34
Q

Aplastic anemia results from ____ or ____

A

Aplastic anemia results from T-cell mediated autoimmune processes or acute hematopoietic stem cell damage by drugs / high dose radiation

35
Q

Aplastic anemia presents with ____, ____, and ____

A

Aplastic anemia presents with pancytopenia, normal cytogenetics / cell morphology, and evolution to empty marrow

36
Q

Hematopoietic stem cell transplantation requires ____

A

Hematopoietic stem cell transplantation requires close matching

  • Ideally sibling donor, HLA matched unrelated donor possible for younger patients
  • Complications: graft failure / lack of engraftment, graft vs host disease (transplanted marrow rejects recipient)

Heme / Onc (41 decks)

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