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HEMATOLOGY 2 > MIDTERM LECTURE L1: ACUTE LYMPHOBLASTIC LEUKEMIA > Flashcards

MIDTERM LECTURE L1: ACUTE LYMPHOBLASTIC LEUKEMIA Flashcards

1
Q

The broad term “leukemia” is derived from what ancient Greek words?

A

leukos (white) and haima (blood)

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2
Q

Refers to the rapid clonal proliferation in the bone marrow of lymphoid or myeloid progenitor cells

A

acute leukemia

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3
Q

Acute leukemia is the rapid clonal proliferation in the bone marrow of progenitor cells known as?

A

lymphoblasts (lymphocytes) and myeloblasts (neutrophil)

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4
Q

When proliferation of blasts overwhelms the bone marrow, the blasts are seen in the?

A

peripheral blood

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5
Q

Most causes of the development of malignancy are

A

unknown

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6
Q

Some of the known causes of leukemia include

A
  • exposure to organic solvent (e.g. benzene)
  • familial cancer predisposition syndromes
  • alkylating agents and other forms of chemotherapy
  • radiation
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7
Q

Alkylating agents and other forms of chemotherapy could result to what type of leukemia?

A

therapy-related leukemia

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8
Q

Development of leukemia is best believed due to progression of mutations or “___________” that hinders proliferation

A

multiple hits

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9
Q

In leukemia, hematopoietic stem cells become what kind of cells?

A

Leukemic stem cells
(LSCs)

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10
Q

Leukemic stem cell continuous to proliferate, but forgets how to mature and differentiate due to what 2 reasons?

A
  • genetic deletion
  • genetic inhibition
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11
Q

Initiate, proliferate, and sustain the leukemia (full of blasts)

A

Leukemic stem cells (LSCs)

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12
Q

2 types of classification schemes for acute leukemia

A
  • French-American-British (FAB) classification
  • WHO classification
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13
Q

In FAB classification, lymphoblasts and myeloblasts are distinguished based on

A

morphological examination along with cytochemical stains

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14
Q

FAB classification was devised in what year?

A

1970s

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15
Q

Techniques commonly used to diagnose hematopoietic malignancies

A

flow cytometry and genetic/molecular studies

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16
Q

According to WHO classification, to diagnose the majority of acute leukemias, there must be at least how many percent of blasts in the bone marrow?

A

20%

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17
Q

Leukemia that is primarily a disease of childhood and adolescence

A

Acute Lymphoblastic Leukemia (ALL)

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18
Q

Acute lymphoma can either be?

A

T cell ALL or B cell ALL

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19
Q

The peak incidence of ALL in children is between what ages?

A

2-5 years

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20
Q

Most adult patients of ALL are older than what age

A

older than 50 years of age

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21
Q

How many percent of adults with ALL experience complete remission?

A

80-90%

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22
Q

Cure rate of adults with ALL is less than how many percent?

A

<40%

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23
Q

An important prognostic indicator for survival

A

subtype of ALL

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24
Q

Patients with B cell ALL typically present with what symptoms? (enumerate)

A

● Fatigue (anemia)
● Fever (neutropenia & infection)
● Mucocutaneous bleeding
(thrombocytopenia)
● Lymphadenopathy
● Splenomegaly & Hepatomegaly
(infiltration of malignant
cells and extramedullary
hematopoiesis-present to
compensate the inability of BM to produce other cell)
● Bone Pain
(intramedullary growth of leukemic cells)

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25
Q

T cell ALL presents with the same symptoms, although the degree of leukopenia is often (less/more?) severe

A

LESS

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26
Q

2 morphologic types of lymphoblast

A

small lymphoblast and large lymphoblast

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27
Q

The most common morphologic type of lymphoblast

A

small lymphoblast

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28
Q

With prominent nucleoli and nuclear membrane irregularities

A

large lymphoblast

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29
Q

With scant blue cytoplasm and indistinct nucleoli

A

small lymphoblast

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30
Q

The small lymphoblast is how many times larger than the normal lymphocyte

A

1.0-2.5x than normal lymphocyte

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31
Q

The large lymphoblast is how many times larger than the normal lymphocyte?

A

2-3x than normal lymphocyte

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32
Q

The prognosis of ALL depends on

A
  • age at the time of diagnosis
  • lymphoblastic load (tumor burden)
  • immunophenotype
  • genetic abnormalities
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33
Q

T/F: ALL is common in adults

A

F (it is rare)

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34
Q

T/F: ALL is rare in adults, but risk increases with age

A

T

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35
Q

Who has a poorer outlook of ALL, the children or adults?

36
Q

This mutation is the strongest prediction of adverse treatment outcomes

A

chromosomal translocation

37
Q

Peripheral blood lymphoblast count that is associated with worse outcomes

A

> 20-30x10^9/L

38
Q

Other symptoms associated with worse outcomes (aside from >20-30x10^9/L lymphoblast count)

A
  • hepatosplenomegaly
  • lymphadenopathy
39
Q

The most reliable indicators of a cell’s origin

A

immunophenotyping and genetic analysis

40
Q

The first tool used to distinguish ALL from AML

A

immunophenotyping

41
Q

4 types of ALL

A

● Early (pro/pre-pre) B-ALL
● Intermediate (common) B-ALL
● Pre-B-ALL
● T-ALL

42
Q

Both B and T cell are derived from lymphoid progenitors, and both usually express?

A
  • CD34
  • Terminal deoxynucleotidyl transferase (TdT)
  • Human leukocyte antigen, DR subregion (HLA-DR)
43
Q

Characterized by specific B cell antigens that are expressed at different stages of B cell development

44
Q

In general B cells expresses

A
  • CD10
  • CD19
  • CD20
  • CD22
  • CD24
  • CD79a
  • cytoplasmic μ
  • PAX-5
45
Q

Other name for CD10

A

common acute lymphoblastic leukemia antigen

or

common acute leukemic leukemia antigen

46
Q

B cell specific activator protein

47
Q

Early (pre-pre-/pro) B-ALL expresses?

A
  • CD34
  • CD19
  • cytoplasmic CD22
  • terminal deoxynucleotidyl transferase (TdT)
48
Q

Intermediate (common) B-ALL expresses?

A
  • CD34
  • CD19
  • cytoplasmic CD22
  • terminal deoxynucleotidyl transferase (TdT)
  • CD10
49
Q

Pre-B-ALL expresses?

A
  • CD34
  • CD19
  • cytoplasmic CD22
  • TdT (variable)
  • Cytoplasmic μ
50
Q

T-ALL expresses most of the common T cell markers which are

A
  • CD2
  • CD3
  • CD4
  • CD5
  • CD7
  • CD8
  • TdT (most cases express this)
51
Q

The most mature B-ALL is called

52
Q

In pre-B-ALL, CD34 is typically

53
Q

Incidence of pro-B-ALL is about how many percent in children?

A

5% in children

54
Q

Incidence of pro-B-ALL is about how many percent in adults?

A

11% in adults

55
Q

Pre-B-ALL accounts for how many percent of childhood cases?

56
Q

Pre-B-ALL accounts for how many percent of adult B-ALL?

57
Q

T/F: T-ALL is most often teenage females

A

F (teenage males)

58
Q

T cell ALL is seen most often in teenage males with

A
  • mediastinal mass
  • elevated peripheral blast count
  • meningeal involvement
  • infiltration of extra marrow sites
59
Q

A distinct subtype of T-ALL that often shows expression of myeloid markers and was thought to have the capacity for myeloid differentiation

A

Early T cell precursor ALL (ETP-ALL)

60
Q

What year did WHO classification subcategorizes T-ALL into ETP-ALL?

61
Q

T/F: ETP-ALL has poor prognosis to therapy

62
Q

Majority of T-ALL have been shown to have gain-of-function mutations involving what gene?

A

NOTCH1 gene

63
Q

Mutations in NOTCH1 gene alters Notch receptor signaling pathway which is responsible for

A

normal T cell development

64
Q

In T-ALL, the cytogenetic alterations show (less/more?) specificity and (less/more?) correlation with the prognosis and treatment outcome than in B-ALL

65
Q

according to WHO classification, B-lymphoblastic leukemia (B-ALL) is subdivided into how many subtypes?

66
Q

9 subtypes of B-ALL

A

● B-ALL with t(9;22)(q34.1;q11.2);BCR-ABL1
● B-ALL with t(v;11q23.3);KMT2A (MLL) rearranged
● B-ALL with t(12;21)(p13.2;q22.1);TEL-AML1 (ETV6-RUNX1)
● B-ALL with hyperdiploidy
● B-ALL with hypodiploidy
● B-ALL with t(5;14)(q31.1;q32.1);IGH/IL3
● B-ALL with t(1;19)(q23;p13.3);TCF3-PBX1 (E2A-PBX1)
● B-ALL, BCR-ABL1-like
● B-ALL with iAMP21

67
Q

The 9 subtypes of B-ALL are linked with

A
  • unique clinical, phenotypic, or prognostic features
68
Q

B-ALL that do not exhibit specific genetic abnormalities

A

B-lymphoblastic leukemia/lymphoma, not otherwise
specified

69
Q

The mutation in B-ALL with the t(9;22)(q34.1;q11.2)

A

BCR-ABL1 mutation

70
Q

Chromosome that has the worst prognosis among ALLs

A

Philadelphia chromosome–positive ALL

71
Q

T/F: BCR-ABL1 mutation (Philadelphia chromosome–positive ALL) is more common in children

A

F (more common in adults)

72
Q

Mutation in B-ALL with t(v;11q23)

A

KMT2A(MLL)-rearranged

73
Q

Mutation in t(12;21)(p13.2;q22.1)

A

ETV6-RUNX1 translocation (childhood ALL)

74
Q

Common in very young infants and has a very poor prognosis

A

B-ALL with t(v;11q23); KMT2A(MLL)-rearranged

75
Q

t(12;21)(p13.2;q22.1);ETV6-RUNX1
translocation, accounts for how many percent of childhood ALL cases?

76
Q

Cure rate of t(12;21)(p13.2;q22.1);ETV6-RUNX1
translocation

77
Q

T/F: t(12;21)(p13.2;q22.1);ETV6-RUNX1
translocation is rare in adults

78
Q

In B-ALL with t(v;11q23); KMT2A(MLL)- rearranged, the translocation may occur in

79
Q

T/F: Cytogenetic abnormalities are seen in the majority of B cell ALL only

A

F
(seen in the majority of B and T cell ALL)

80
Q

Greater than 46 chromosomes and has a very favorable prognosis in children

A

hyperdiploidy

81
Q

Less that 46 chromosomes and has poor prognosis in both children and adults

A

hypodiploidy

82
Q

B-ALL with hyperdiploidy is common in childhood B-ALL, accounting to how many percent of cases?

83
Q

T/F: 50-70% of patients with T-lymphoblastic leukemia have abnormal gene rearrangement, but none of the abnormalities are associated with specific biologic features

84
Q

Has limited early T cell differentiation

A

early T-cell precursor ALL (ETP-ALL)

85
Q

Medicine that has shown success in treating chronic myeloid leukemia and has improved survival

HEMATOLOGY 2 (10 decks)

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