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Heme > Lec 13 Intro to WBC > Flashcards

Lec 13 Intro to WBC Flashcards

1
Q

What are the origin myeloid malignancies?

A

involve cells of myeloid lineage [granulocytes, monocytes/ macrophages, erythrocytes, megakaryocytes/ platelets]

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2
Q

What is an acute leukemia?

A

leukemia with rapid onset; rapidly progressive and fatal

cells are not well differentiated or mature

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3
Q

What is a chronic leukemia?

A

leukemia with insidious onset

cells are mature and well differentiated

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4
Q

In leukemia are the malignant cells in the bone marrow or peripheral blood?

A

both!

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5
Q

What does it mean to have extramedullary disease?

A

leukemic cells infiltrate CNS, skin, liver, splee, lymph nodes

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6
Q

What characterizes acute leukemias?

A

clonal [from single transformed cell], characterized by impaired differentiation of hematopoietic cells; failure of apoptosis

have leukemic stem cells with self renewal capacity

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7
Q

What mech causes resistance to chemotherapy + relapse in leukemia?

A

evolution of sub-clones with additional mutations

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8
Q

What are some signs of acute leukemia?

A

anemia, hemorrhage, infection b/c the normal hematopoietic cells are crowded out by the accumulation of immature poorly functioning leukemic cells

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9
Q

What is acute myelogenous leukemia?

A

acute leukemia from myeloid lineage

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10
Q

What is median age of AML?

A

70 years old

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11
Q

What is acute lymphocytic leukemia [ALL]?

A

leukemia characterized by lymphoid lineage markers

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12
Q

Who gets ALL?

A

can be seen in chidlhood but can occur at any age

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13
Q

What are risk factors for acute leukemia?

A
  • benzene exposure
  • ionizing radiation
  • prior exposure to chemo
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14
Q

What are some inherited risks for acute leukemia?

A
  • down’s syndrome
  • fanconi anemia
  • bloom’s syndrome
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15
Q

What types of mutations associated with acute leukemias?

A
  • structural chromosomal abnormalities [deletions, translocations], somatic mutations
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16
Q

How many subtypes of AML and ALL are there?

A

8 types of AML

3 types of ALL

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17
Q

What is a leukemia vs lymphoma?

A

leukemia = malignant cells in blood and marrow and can invade other organs

lymphoma = malignant cells confined to nodes/spleen; can sometimes invade blood and marrow and other organs

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18
Q

What are some underlying causes that can lead to secondary acute myelogenous leukemia?

A
  • aplastic anemia
  • paroxysmal nocturnal hemoglobinuria
  • myelodysplasia
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19
Q

What is definition of acute leukemia?

A

> 30% blasts in blood or bone marrow

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20
Q

What is the strongest predictor of response to induction and survival?

A

cytogenetics

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21
Q

M2 AML is associated wtih what chromosomal translocation? What kind of prognosis?

A

(8;21) pretty good prognosis

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22
Q

What do you see on labs in acute leukemia?

A
  • 50% normal or low WBC
  • neutropenia
  • hyperleukocytosis
  • thrombocytopenia
  • anemia
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23
Q

What chromosomal abnormality in M3 type of AML?

A

chromosome translocation (15;17)

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24
Q

What do you see on smear in M3 AML?

A

auer rods = cytoplasmic inclusions

lots of circulating myeloblasts

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25
What is a possible complication of M3 AML?
development of DIC
26
How do you treat M3 AML?
all-trans retinoic acid [vit A] --> induces differentiation of myeloblasts
27
What type of chromosomal rearrangement in M4 AML?
inversion of chromosome 16
28
What do you see clinically in the M4 and M5 AML subtypes?
high white cells counts; extramedullary invovlement --> gingival hypertrophy + CNS involvement
29
What are some complications of acute leukemia?
- infection secondary to neutropenia --> candida, cellulitis, herpes zoster - bleeding --> thrombocytopenia and DIC
30
What types of chromosome abnormalities in M3 AML?
abnormalities in chromosomes 5q and 7q
31
What subtype of ALL often seen in childhood ALL?
L1
32
What is the burkitt type of ALL?
L3
33
What happens in hyperleukocytosis in acute leukemia?
leukemic blast cells counts > 50,000 --> get leukostasis = the blast cells obstruct small blood vessels in CNS and lungs --> intracranial hemorrhage, hypoxemia, headaches
34
What types of leukemia most likely to see organ infiltration?
ALL and M4/M5 subtypes of AML
35
What lab findings in leukemia?
high urinc acid level b/c of increased cell turnover
36
What do you see in bone marrow aspirate in acute leukemia?
hypercellular normal hematopoietic cells replaced by monotonous population of immature cells; megakaryocytes decreased in number may get dry tap b/c marrow so packed/sticky
37
What morphologic features distinguish myeloid from lymphoid leukemia?
presence of auer rod in myeloid leukemia; no auer rod in ALL
38
What does positive myeloperoxidase stain tell you?
tells you AML
39
What does positive sudan black stain tell you?
tells you AML
40
What does positive PAS stain tell you?
positive in ALL and erythroid leukemia AML- M6
41
What do you see in pre-B cell ALL?
- arise from early lymphoid progenitor - express CALLA antigen [CD10] - express cytoplasmic Ig - TdT [terminal deoxynucleotidyl transferase]
42
What is prognosis fo CALLA type ALL?
good prognosis, seen in kids
43
What do you see in B cell ALL?
- known as burkitt's type - L3 morphology - positive surface Ig expression - chromosome translocation (8;14) - TdT negative
44
What do you see in T cell ALL?
- T cell markers - positive TdT stain - chromosomal translocation (11; 14) - identical to lymphoblastic lymphoma
45
What types of ALL have TdT [terminal deoxynucleotidy transferase]?
CALLA positive ALL T cell ALL T cell lymphoblastic lymphoma
46
t(9;22) is associated with what disorder? what is the gene involved?
CML | this is philadelphia chromosome = get bcr-abl hybrid
47
t(8;14) is associated with what disorder? what is the gene involved?
Burkitt lymphoma get c-myc activation
48
t(11;14) is associated with what disorder? what is the gene involved?
mantle cell lymphoma get cyclin D1 activation
49
t(14;18) is associated with what disorder? what is the gene involved?
follicular lymphoma get bcl-2 activation
50
t(15;17) is associated with what disorder? what is the gene involved?
M3 type of AML get destruction of retinoic acid gene; responds to all-trans retinoic acid
51
How can FISH and PCR be used in leukemia?
- to detect presence of a specific abnormality - to follow response to therapy - to detect evidence of recurrence
52
What are myelodyplastic syndromes?
clonal stem cell disease with hypercellular marrow and trilineage dysplasia; at risk for evolution to acute leukemia
53
What is treatment for myelodysplasia?
allogenic stem cell transplantation
54
What are pelger huet cells? what do they suggest?
they are hyposegmented neutrophils | suggest myelodysplastic syndrome
55
What is significance of Fms-like tyrosine kinase 3 [FLT3]?
mutated in 1/3 of patients with normal cytogenics AML; associated wtih increased risk of relapse and poorer survival
56
What is significance of wilm's tumor [WT1] gene?
mutated in some pts with normal cytogenetics AML; associated with poorer prognosis
57
What is significance of nucleophosmin [NPM1] gene?
mutated in 50% of pts with normal cytogenetics AML; associated with higher WBC count, higher remission rates, reduced relapse risk
58
What is significance of CEBPa gene?
mutation see in normal cytogenetics AML; associated with better prognosis
59
What is significance of C-kit gene mutations?
see with pts with AML; have owrse prognosis
60
What is prognosis of majority of adult leukemia pts?
most relapse b/c not all leukemic stem cells are eradicated
61
What is purpose of induction therapy?
intended to achieve a complete remission
62
What is purpose of post remission therapy?
prevent relapse
63
What is standard induction chemo regimen for AML?
7+3
64
What are some complications of induction therapy?
N/V, diarrhea, skin damage, neuro tox, BM aplasia --> anemia, thrombocytopenia, neutropenia
65
What is tumor lysis syndrome?
when many leukemic cells lysed by chemo at same time --> metabolic waste products release --> hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and renal failure
66
What are some targeted treatments for AML M3 type [acute promyelocytic leukemia]?
- all-trans-retinoic acid [ATRA] --> induces differentiation/maturation of promyeloblasts - arsenic trioxide [ATO] --> induces apoptosis

Heme (20 decks)

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