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]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is an acute leukemia?

A

leukemia with rapid onset; rapidly progressive and fatal

cells are not well differentiated or mature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a chronic leukemia?

A

leukemia with insidious onset

cells are mature and well differentiated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

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

A

both!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does it mean to have extramedullary disease?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What mech causes resistance to chemotherapy + relapse in leukemia?

A

evolution of sub-clones with additional mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is acute myelogenous leukemia?

A

acute leukemia from myeloid lineage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is median age of AML?

A

70 years old

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is acute lymphocytic leukemia [ALL]?

A

leukemia characterized by lymphoid lineage markers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Who gets ALL?

A

can be seen in chidlhood but can occur at any age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are risk factors for acute leukemia?

A
  • benzene exposure
  • ionizing radiation
  • prior exposure to chemo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some inherited risks for acute leukemia?

A
  • down’s syndrome
  • fanconi anemia
  • bloom’s syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What types of mutations associated with acute leukemias?

A
  • structural chromosomal abnormalities [deletions, translocations], somatic mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How many subtypes of AML and ALL are there?

A

8 types of AML

3 types of ALL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

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

A
  • aplastic anemia
  • paroxysmal nocturnal hemoglobinuria
  • myelodysplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is definition of acute leukemia?

A

> 30% blasts in blood or bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

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

A

cytogenetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

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

A

(8;21) pretty good prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do you see on labs in acute leukemia?

A
  • 50% normal or low WBC
  • neutropenia
  • hyperleukocytosis
  • thrombocytopenia
  • anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What chromosomal abnormality in M3 type of AML?

A

chromosome translocation (15;17)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What do you see on smear in M3 AML?

A

auer rods = cytoplasmic inclusions

lots of circulating myeloblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is a possible complication of M3 AML?

A

development of DIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How do you treat M3 AML?

A

all-trans retinoic acid [vit A] –> induces differentiation of myeloblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What type of chromosomal rearrangement in M4 AML?

A

inversion of chromosome 16

28
Q

What do you see clinically in the M4 and M5 AML subtypes?

A

high white cells counts; extramedullary invovlement –> gingival hypertrophy + CNS involvement

29
Q

What are some complications of acute leukemia?

A
  • infection secondary to neutropenia –> candida, cellulitis, herpes zoster
  • bleeding –> thrombocytopenia and DIC
30
Q

What types of chromosome abnormalities in M3 AML?

A

abnormalities in chromosomes 5q and 7q

31
Q

What subtype of ALL often seen in childhood ALL?

A

L1

32
Q

What is the burkitt type of ALL?

A

L3

33
Q

What happens in hyperleukocytosis in acute leukemia?

A

leukemic blast cells counts > 50,000 –> get leukostasis = the blast cells obstruct small blood vessels in CNS and lungs

–> intracranial hemorrhage, hypoxemia, headaches

34
Q

What types of leukemia most likely to see organ infiltration?

A

ALL and M4/M5 subtypes of AML

35
Q

What lab findings in leukemia?

A

high urinc acid level b/c of increased cell turnover

36
Q

What do you see in bone marrow aspirate in acute leukemia?

A

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
Q

What morphologic features distinguish myeloid from lymphoid leukemia?

A

presence of auer rod in myeloid leukemia; no auer rod in ALL

38
Q

What does positive myeloperoxidase stain tell you?

A

tells you AML

39
Q

What does positive sudan black stain tell you?

A

tells you AML

40
Q

What does positive PAS stain tell you?

A

positive in ALL and erythroid leukemia AML- M6

41
Q

What do you see in pre-B cell ALL?

A
  • arise from early lymphoid progenitor
  • express CALLA antigen [CD10]
  • express cytoplasmic Ig
  • TdT [terminal deoxynucleotidyl transferase]
42
Q

What is prognosis fo CALLA type ALL?

A

good prognosis, seen in kids

43
Q

What do you see in B cell ALL?

A
  • known as burkitt’s type
  • L3 morphology
  • positive surface Ig expression
  • chromosome translocation (8;14)
  • TdT negative
44
Q

What do you see in T cell ALL?

A
  • T cell markers
  • positive TdT stain
  • chromosomal translocation (11; 14)
  • identical to lymphoblastic lymphoma
45
Q

What types of ALL have TdT [terminal deoxynucleotidy transferase]?

A

CALLA positive ALL
T cell ALL
T cell lymphoblastic lymphoma

46
Q

t(9;22) is associated with what disorder? what is the gene involved?

A

CML

this is philadelphia chromosome = get bcr-abl hybrid

47
Q

t(8;14) is associated with what disorder? what is the gene involved?

A

Burkitt lymphoma

get c-myc activation

48
Q

t(11;14) is associated with what disorder? what is the gene involved?

A

mantle cell lymphoma

get cyclin D1 activation

49
Q

t(14;18) is associated with what disorder? what is the gene involved?

A

follicular lymphoma

get bcl-2 activation

50
Q

t(15;17) is associated with what disorder? what is the gene involved?

A

M3 type of AML

get destruction of retinoic acid gene; responds to all-trans retinoic acid

51
Q

How can FISH and PCR be used in leukemia?

A
  • to detect presence of a specific abnormality
  • to follow response to therapy
  • to detect evidence of recurrence
52
Q

What are myelodyplastic syndromes?

A

clonal stem cell disease with hypercellular marrow and trilineage dysplasia; at risk for evolution to acute leukemia

53
Q

What is treatment for myelodysplasia?

A

allogenic stem cell transplantation

54
Q

What are pelger huet cells? what do they suggest?

A

they are hyposegmented neutrophils

suggest myelodysplastic syndrome

55
Q

What is significance of Fms-like tyrosine kinase 3 [FLT3]?

A

mutated in 1/3 of patients with normal cytogenics AML; associated wtih increased risk of relapse and poorer survival

56
Q

What is significance of wilm’s tumor [WT1] gene?

A

mutated in some pts with normal cytogenetics AML; associated with poorer prognosis

57
Q

What is significance of nucleophosmin [NPM1] gene?

A

mutated in 50% of pts with normal cytogenetics AML; associated with higher WBC count, higher remission rates, reduced relapse risk

58
Q

What is significance of CEBPa gene?

A

mutation see in normal cytogenetics AML; associated with better prognosis

59
Q

What is significance of C-kit gene mutations?

A

see with pts with AML; have owrse prognosis

60
Q

What is prognosis of majority of adult leukemia pts?

A

most relapse b/c not all leukemic stem cells are eradicated

61
Q

What is purpose of induction therapy?

A

intended to achieve a complete remission

62
Q

What is purpose of post remission therapy?

A

prevent relapse

63
Q

What is standard induction chemo regimen for AML?

A

7+3

64
Q

What are some complications of induction therapy?

A

N/V, diarrhea, skin damage, neuro tox, BM aplasia –> anemia, thrombocytopenia, neutropenia

65
Q

What is tumor lysis syndrome?

A

when many leukemic cells lysed by chemo at same time –> metabolic waste products release –> hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and renal failure

66
Q

What are some targeted treatments for AML M3 type [acute promyelocytic leukemia]?

A
  • all-trans-retinoic acid [ATRA] –> induces differentiation/maturation of promyeloblasts
  • arsenic trioxide [ATO] –> induces apoptosis