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03. Lymphoreticular Pathology > 3. Leukemias > Flashcards

3. Leukemias Flashcards

1
Q

Definition of leukemias

A

Malignancies of the hematopoietic system which are primarily disorders of the bone marrow, presenting with widespread involvement of the bone marrow; no discrete tumour mass is formed; usually with large numbers of tumour cells circulating in the peripheral blood

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2
Q

Progression of leukemia

A
  1. Leukemic cells originate within the bone marrow
    - Usually overgrows the normal bone marrow cells
    - Replaces normal hypercellularity (many cell types)
    with monotony (1 predominant neoplastic cell type)
  2. Leukemic cells usually spill from the bone marrow into
    the blood, where they may be seen in large numbers
    - Acute leukemias tend to present with blast (primitive looking; high nuclear: cytoplasmic ratio, prominent
    nucleolus) cells in peripheral blood
    - Chronic leukemias tend to present with less
    primitive-looking neoplastic white cells in peripheral
    blood
  3. Leukemic cells may also infiltrate lymph nodes, liver,
    spleen & other tissues, causing secondary organomegaly
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3
Q

Classification of leukemias

A
  1. Acute lymphoblastic leukemia (ALL)
  2. Acute myelogenous leukemia (AML)
  3. Chronic lymphocytic leukemia (CLL)
  4. Chronic myelogenous leukemia (CML)
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4
Q

Cell of origin of acute lymphoblastic leukemia

A

precursor B or T cell

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5
Q

Frequency & association of acute lymphoblastic leukaemia

A

Rare, but most common cancer of children (peak

incidence at age 3)

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6
Q

Immunophenotype of acute lymphoblastic leukemia

A
  1. [B-ALL] CD10+, CD19+, CD20+

2. [T-ALL] CD1+, CD2+, CD5+, CD7+

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7
Q

Prognostic factors for acute lymphoblastic leukemia

A
  1. t(9;22) (bad prog.)
  2. t(12;21) (good prog.)
  3. Hyperdiploid (good prog.)
  4. Peripheral white cell counts (low = good prog.)
  5. Age (2-10 = good prog.; <2 or >10 = bad prog.)
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8
Q

Clinical features of acute lymphoblastic leukemia

A
  1. Symptoms of depressed marrow function
  2. Mass effects of neoplastic infiltration (bone pain, generalised lymphadenopathy)
  3. CNS effects due to meningeal involvement (headache, vomiting, nerve palsies)
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9
Q

Cell of origin of acute myelogenous leukemia

A

Hematopoietic precursor cell

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10
Q

Frequency & association of acute myelogenous leukemia

A

Can affect children or adults

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11
Q

Pathogenesis of acute myelogenous leukemia

A

Caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blast cells in the marrow

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12
Q

Clinical features of acute myelogenous leukemia

A

Clinical features: similar to those of ALL

- Rapidly fatal without treatment

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13
Q

Cell of origin of chronic lymphocytic leukemia

A

peripheral B cells (naïve or memory)

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14
Q

Frequency & associations of chronic lymphocytic leukemia

A
  1. Represents approximately 1/3 of all leukemias

2. Primarily a disease of the elderly (median age = 65)

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15
Q

Immunophenotype of chronic lymphocytic leukemia

A
  1. CD5+, CD19+, CD20+, CD23+

2. Low level of surface Ig expression

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16
Q

Molecular signature of chronic lymphocytic leukemia

A

None, note that unlike most other lymphoid malignancies, chromosomal translocations are rare in CLL

17
Q

Prognostic factors for chronic lymphocytic leukemia

A
  1. Lack of somatic hypermutation (poor prog.)

2. Deletions of 11q & 17p (poor prog.)

18
Q

Clinical features of chronic lymphocytic leukemia

A
  1. Asymptomatic
  2. Non-specific symptoms: easy fatiguability, anorexia, weight loss
  3. Generalized lymphadenopathy
  4. Hepatosplenomegaly
  5. Leukopenia (with marrow involvement) or
    leukocytosis (with heavy tumour burden)
  6. Transformation in DLBCL in some patients
19
Q

Cell of origin of chronic myelogenous leukemia

A

Myeloid cell

20
Q

Frequency & associations of chronic myelogenous leukemia

A

Disease of middle age, may occur in young children

21
Q

Molecular signature of chronic myelogenous leukemia

A

t(9;22) → Philadelphia chromosome, encodes BCR-ABL chimeric tyrosine kinase

22
Q

Clinical features of chronic myelogenous leukemia

A
  1. Indolent chronic phase (4-6 years)
  2. Subsequently progressed to an accelerated
    phase & then an acute blastic phase (6-18
    months)
  3. Can treat with imatinib mesylate (a tyrosine
    kinase inhibitor)
23
Q

Clinical presentations in acute leukemias

A
  1. Fatigue (due to anemia)
  2. Fever & infection (due to leukocytopenia)
  3. Bleeding tendencies (due to thrombocytopenia)
  4. Usually fatal within weeks if left untreated
24
Q

Clinical presentations in chronic leukemias

A
  1. Fatigue, weight loss, anemia
  2. Abnormal sensation in the abdomen (due to
    splenomegaly)
  3. Patients with untreated chronic leukemia usually
    live longer than those with untreated acute leukemia

03. Lymphoreticular Pathology (5 decks)

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