MIDTERM LECTURE L1: ACUTE LYMPHOBLASTIC LEUKEMIA Flashcards by Denzeline Go

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

leukos (white) and haima (blood)

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

acute leukemia

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

lymphoblasts (lymphocytes) and myeloblasts (neutrophil)

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

peripheral blood

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Most causes of the development of malignancy are

unknown

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Some of the known causes of leukemia include

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

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

therapy-related leukemia

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

multiple hits

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

Leukemic stem cells
(LSCs)

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

genetic deletion
genetic inhibition

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

Leukemic stem cells (LSCs)

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2 types of classification schemes for acute leukemia

French-American-British (FAB) classification
WHO classification

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In FAB classification, lymphoblasts and myeloblasts are distinguished based on

morphological examination along with cytochemical stains

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FAB classification was devised in what year?

1970s

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Techniques commonly used to diagnose hematopoietic malignancies

flow cytometry and genetic/molecular studies

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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?

20%

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Leukemia that is primarily a disease of childhood and adolescence

Acute Lymphoblastic Leukemia (ALL)

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Acute lymphoma can either be?

T cell ALL or B cell ALL

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

2-5 years

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Most adult patients of ALL are older than what age

older than 50 years of age

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How many percent of adults with ALL experience complete remission?

80-90%

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

<40%

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An important prognostic indicator for survival

subtype of ALL

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

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

LESS

2 morphologic types of lymphoblast

small lymphoblast and large lymphoblast

The most common morphologic type of lymphoblast

small lymphoblast

With prominent nucleoli and nuclear membrane irregularities

large lymphoblast

With scant blue cytoplasm and indistinct nucleoli

small lymphoblast

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

1.0-2.5x than normal lymphocyte

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

2-3x than normal lymphocyte

The prognosis of ALL depends on

- age at the time of diagnosis - lymphoblastic load (tumor burden) - immunophenotype - genetic abnormalities

T/F: ALL is common in adults

F (it is rare)

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

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

adults

This mutation is the strongest prediction of adverse treatment outcomes

chromosomal translocation

Peripheral blood lymphoblast count that is associated with worse outcomes

>20-30x10^9/L

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

- hepatosplenomegaly - lymphadenopathy

The most reliable indicators of a cell's origin

immunophenotyping and genetic analysis

The first tool used to distinguish ALL from AML

immunophenotyping

4 types of ALL

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

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

- CD34 - Terminal deoxynucleotidyl transferase (TdT) - Human leukocyte antigen, DR subregion (HLA-DR)

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

B-ALL

In general B cells expresses

- CD10 - CD19 - CD20 - CD22 - CD24 - CD79a - cytoplasmic μ - PAX-5

Other name for CD10

common acute lymphoblastic leukemia antigen or common acute leukemic leukemia antigen

B cell specific activator protein

PAX-5

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

- CD34 - CD19 - cytoplasmic CD22 - terminal deoxynucleotidyl transferase (TdT)

Intermediate (common) B-ALL expresses?

- CD34 - CD19 - cytoplasmic CD22 - terminal deoxynucleotidyl transferase (TdT) - CD10

Pre-B-ALL expresses?

- CD34 - CD19 - cytoplasmic CD22 - TdT (variable) - Cytoplasmic μ

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

- CD2 - CD3 - CD4 - CD5 - CD7 - CD8 - TdT (most cases express this)

The most mature B-ALL is called

pre-B-ALL

In pre-B-ALL, CD34 is typically

negative

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

5% in children

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

11% in adults

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

15%

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

10%

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

F (teenage males)

T cell ALL is seen most often in teenage males with

- mediastinal mass - elevated peripheral blast count - meningeal involvement - infiltration of extra marrow sites

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

Early T cell precursor ALL (ETP-ALL)

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

2017

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

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

NOTCH1 gene

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

normal T cell development

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

less less

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

9 subtypes of B-ALL

● 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

The 9 subtypes of B-ALL are linked with

- unique clinical, phenotypic, or prognostic features

B-ALL that do not exhibit specific genetic abnormalities

B-lymphoblastic leukemia/lymphoma, not otherwise specified

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

BCR-ABL1 mutation

Chromosome that has the worst prognosis among ALLs

Philadelphia chromosome–positive ALL

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

F (more common in adults)

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

KMT2A(MLL)-rearranged

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

ETV6-RUNX1 translocation (childhood ALL)

Common in very young infants and has a very poor prognosis

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

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

25%

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

90%

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

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

utero

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

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

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

hyperdiploidy

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

hypodiploidy

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

25%

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

Has limited early T cell differentiation

early T-cell precursor ALL (ETP-ALL)

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

imatinib

MIDTERM LECTURE L1: ACUTE LYMPHOBLASTIC LEUKEMIA Flashcards

(85 cards)