Acute Leukemia Flashcards by Zachary Stielper

What is the definition of leukemia?

A progressive, malignant disease of the blood-forming organs, marked by distorted proliferation and development of WBCs and their precursors; primarily involving the bone marrow and blood

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What is the major difference between leukemia and lymphoma?

Site of involvement

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What do acute and chronic mean when in reference to leukemias or lymphomas?

Acute indicates that the neoplasm is of immature cells while chronic neoplasms are of mature cells

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Why is acute leukemia bad?

There is a block in maturation of a cell lineage in the bone marrow and proliferation of those immature cells accompanied by insuficient apoptosis

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What are the differences between acute leukemia an myelodysplasia?

With acute leukemia there is a block in maturation, increased proliferation with decreased apoptosis; in myelodysplasis there is also ineffective maturation but there is increased apoptosis within the bone marrow

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What is the most common presenting sign of leukemia?

Peripheral cytopenia

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What are the clinical findings associated with leukemias?

Peripheral cytopenia, splenomegaly, hepatomegaly, lymphadenopathy, systemic (“B”) symptoms (fatigue, fever, malaise, weight loss), and metabolic alterations

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What antigens are used for immunophenotyping myeloid differentiation?

CD33, 13, 14, 64, myeloperoxidase

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What antigens are used for immunophenotyping T-cell differentiation?

CD3, 4, 5, 7, 8

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What antigens are used for immunophenotyping B-cell differentiation?

CD19, 20, 22, 79a

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What antigens are used for immunophenotyping immature cells?

CD34, 117, TdT

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What is the threshold that differentiates Acute from Chronic leukemia?

Greater than 20% of blasts in the bone marrow or peripheral blood indicates a significant block in maturation and an acute process

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What are two basic subcategories of Acute Leukemia?

Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia

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In what kind of acute leukemia may auer rods be found?

Myelogenous

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What are auer rods?

Aggregates of MPO

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What are the two classes of mutations that must be acquired for development of acute myelogenous leukemia?

Class I (Increased proliferation or survival) and Class II (Impaired differentiation or apoptosis)

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What are the subclassifications of AML?

AML w/ recurrant cytogenetic abnormalities; AML w/ myelodysplasia-related changes; Myeloid sarcoma; Myeloid proliferation related to Down Syndrome; Blastic plasmacystoid dendritic cell neoplasm; AML not otherwise specified

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What chromosomal translocations are associated with a good AML prognosis?

t(8;21), t(15;17), inv(16)

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What chromosomal translocations are associated with a poor AML prognosis?

11q23, t(6;9), inv(3), t(1;22)

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Are FLT3 mutations generally associated with a better or poorer prognosis?

Poor

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What cytogenetic abnormality is associated with Acute Promyelocytic Leukemia?

t(15;17)

What are the 2 distinct morphological variants of APL?

Classic variant- abundant prominent cytoplasmic granules, bundles of auer rods, low WBC count, wt-FLT3; and Microgranular variant- lack prominent cytoplasmic granuels and few auer rods with high WBC counts, more likely to have FLT3 mutation

Why is APL a medical emergency?

There is a high risk of developing DIC

What APL translocation renders cells resistant to all-trans-retinoic acid?

Partnering with Ch. 11 (PZLF/ZBTB16)

How does all-trans-retinoic acid work in the treatment of acute promyelocytic leukemia?

It overcomes the maturatio nblock at the promyelocyte stage

How does APL increase risk of developing DIC?

It increases expression of fibrinolytic annexin II

What is the characteristic morphology of AML with inv(16)?

Eo-basos; immature cells with chunky granules that look like a combinatino of eosinophils and basophils and are CAE+

MLL abnormalities found at 11q23 can be associated with therapy-related AMLs, especially patients treated with what kind of drug?

Topoisomerase II inhibitors

AML associated with MLL alterations are associated with a good or poor prognosis?

Poor

What is characteristic of the morphology of AML with t(6;9)?

Basophilia

What morphology is associated with AML with inv(3)?

Increased # of small megakaryocytes in bone marrow and thrombocytopenia

What cytogenetic abnormality is associated with Down Syndrome-associated AML?

t(1:22)

What is Transient Abnormal Myelopoiesis?

Condition found in 10% of Down Syndrome babies that originates in utero and present within 3 months of life, but most will clear the blasts and this is just a transient process but about 19% of children with TAM progress to AML M7

True or False: DS pts with M7 AML have a worse prognosis than non-DS AML M7 pts.

False

What is the prognosis of AML with normal cytogenetics?

intermediate prognosis

Which mutations are associated with a good prognosis in AML with normal cytogenetics?

NPM1 and CEBPA

Which mutations are associated with a poor prognosis in AML with normal cytogenetics?

FLT3, high ERG, high BAALC, MLL-PTD

What is FLT3?

TYrosine kinase related to PDGFR

What is NPM1?

Protein that shuttle between the nucleus and cytoplasm

What percentage of AML cases have both NPM1 and FLT3-ITD?

~40%

How can AML vs ALL morphology be distinguished?

Lymphoblasts are smaller than non-lymphoblasts and have very little cytoplasm w/ no prominent nucleoli or auer rods

What is the most important determinant of the biology and prognosis of ALL?

Underlying genetic abnormality

What are the two major WHO categories of ALL?

Precursor B lymphoblastic leukemia and Precursor T lymphoblastic leukemia

If ALL presents with lymphomatous and leukemic components what threshold of blasts must be present for a leukemic diagnosis?

>25% blasts in the blood or BM defines the condition as leukemia

What cytogenetic abnormalities associated with ALL have a good prognosis?

t(12:21), hyperdiploidy, 6q-, t(5;14)

What cytogenetic abnormalities associated with ALL have a poor prognosis?

t(9;22), t(1;19), t(4;11), hypodiploidy

What are indicators of poor T-ALL prognosis?

LY1, Tal1

What are indicator of good T-AL prognosis?

HOX11

When assigning more than one lineage to a single blast population what are the requirements for assigning a myeloid lineage?

Must have MPO OR at least 2 of NSE, CD11c, CD14, CD64, lysozyme

When assigning more than one lineage to a single blast population what are the requirements for assigning a T lineage?

Cytoplasmic CD3 or Surface CD3

When assigning more than one lineage to a single blast population what are the requirements for assigning a B lineage?

Strong CD19 with at least one other (strong) CD79a, CD22, CD10 OR Weak CD19 with 2 other strong