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Blood and Lymph 3 > Acute Leukemias > Flashcards

Acute Leukemias Flashcards

1
Q

What two things need to occur in order for an acute leukemia to develop such that it can outcompete the bone marrow?

A
  1. maturation/differentiation is blocked

2. cells are not dependent on external growth factors (increased autonomy of growth signaling pathways.

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2
Q

Define an acute leukemia.

A

a clonal, neoplastic proliferation of immature myeloid or lymphoid cells

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3
Q

What are the two chemotherapies that cause the biggest risk for developing acute leukemia?

A

DNA alkylating agents and topoisomerase-II

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4
Q

What are the biggest risk factors for acute leukemia?

A

previous chemotherapy (especially DNA alkylating agents and topoisomerase-II) and ionizing radiation

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5
Q

What age group does ALL typically occur in?

A

children (75% of cases occur in kids under 6 years old).

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6
Q

Cell markers are important in the diagnosis of leukemias. What important markers do lymphoblasts have in ALL and what does each marker signify?

A

CD34- a marker of immaturity also expressed in myeloblasts

TdT- a nuclear enzyme that is specific to lymphoblasts (not expressed in myeloblasts or mature lymphocytes).

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7
Q

In B-ALL, the leukemic lymphocytes express B cell markers. Which important markers should they contain and which should they lack?

A

positive- CD19, CD22, and/or CD79a (B-cell lineage antigens)

negative- CD20 and surface immunoglobulin (markers of mature B cells)

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8
Q

What cytogenetic findings can occur with B-ALL?

A

-t(9;22) BCR-ABL1
Not all cases of B-ALL contain the translocation but the ones that do result in the philadelphia chromosome. So we say that the patient is Ph + B-ALL.
-t(12;21) ETV6-RUNX1
-B-ALL with translocations at the MLL gene

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9
Q

How is the t(9;22) BCR-ABL1 translocation different in B-ALL than it is in CML?

A

there is a different breakpoint in the BCR gene. In B-ALL the result is a 190kd fusion protein. In CML it is a 210kd protein (Think B before C, and 190 before 210).

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10
Q

Of the three cytogenetic possibilities associated with B-ALL which one has a very favorable prognosis?

A

t(12;21) ETV6-RUNX1 (the others have a poor prognosis with t(9;22) being the worst).

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11
Q

Why might we find a large mediastinal mass associated with T-ALL?

A

T-ALL often presents with a component of T-LBL. In TLBL the T cells hang out in the thymus and a mass develops there (in the mediastinum).

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12
Q

T-ALL/T-LBL favors what gender?

A

affects males over females

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13
Q

What markers are seen in cells with T-ALL?

A

CD2, CD3, and/or CD7 (these are typical T-lineage antigens)
CD4 and/or CD8 (these tell what kind of T cell the t cell is (helper vs CTL) and both can be expressed concurrently)
CD99 and CD1a (these are antigens only seen in immature T cell and sometimes expressed by T-ALL cells)

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14
Q

ALL has the worst prognosis for what age group?

A

Adults and adolescents (ALL kills Adults and Adolescents (A’s)). Even though affects mostly kids under 6.

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15
Q

AML affects which age group most?

A

adults. ALL affects kids, AML affects adults. L before M kids before adults

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16
Q

How do you diagnose AML?

A

there should be increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood. Exceptions to this rule only in the presence of specific cytogenetic findings.

17
Q

An Auer Rod identifies a cell as what kind?

A

a myeloblast. An Auer rod is an azurophilic granule that forms a small stick-like structure in the cytoplasm… just for your information

18
Q

What markers are typically seen in myeloblasts?

A

CD34- a generic marker of immaturity seen in myeloblasts and lymphoblasts
CD117 (also called C-kit), Myeloperoxidase- these are myeloid antigen markers
Also these cells should be negative for tDt

19
Q

What does it mean if a myeloblast expresses CD64 or CD14?

A

This is indicative of monocytic differentiation where leukemic cells (AML) express antigens typical of monocytes instead of myeloblasts.

20
Q

What does it mean if a myeloblast expresses CD41 or CD61

A

this is indicative of megakaryoblastic differentiation where leukemic cells (AML) express antigens typical of megakaryocytes instead of myeloblasts.

21
Q

A high nucleus:cytoplasm ratio is typical of what kind of cell?

A

blasts

22
Q

There are five kinds of AML, what are they?

A 
t(8;21) RUNX1-RUNX1T1
inv(16) or t(16;16) CBFB-MYH11
t(15;17) PML-RARA
t(1;22) RBM15-MKL1
abnormalities with MLL gene
23
Q

how does t(8;21) RUNX1-RUNX1T1 AML work?

A

RUNX1 encodes alpha unit of core binding factor (CBF). This is a transcription factor needed in hematopoiesis. The fusion blocks transcription of CBF dependent genes and thus blocks differentiation.

24
Q

how does AML with inv(16) or t(16;16) CBFB-MYH11 work? what are typical characteristics?

A

CBFB encodes the beta subunit of core binding factor (CBF). differentiation is prevented.
usually see baso-eos and is termed a myelomonocytic leukemia

25
Q

What is APL? how does it work?

A

a subtype of AML (acute promyelocytic leukemia). promyelocytes predominate instead of blasts.
All APL is t(15;17)
typical morphology is hypergranular

26
Q

How can you treat patients with APL?

A

high dose all trans ATRA. High doses overcomes the wonky RARA receptor.

27
Q

Some cases of APL can lead to what

A

DIC

28
Q

AML t(1;22) is seen in patients with ________ and often shows ______ differentiation.

A

down syndrome

megakaryoblastic

29
Q

what is t-AML and how can you get it?

A

therapy related AML. Results from chemo like topoisomerase-II, alkylating agents, or ionizing radiation.

30
Q

If leukemic cells are monoblastic or monocytic we can expect to see problems in what part of the body?

A

gums and skin. leukemic monocytes get into tissues.

31
Q

For each type of leukemia name what type of cells are the leukemic cells:
Myeloid
Myelomonocytic
monoblastic/monocytic

A

myeloblasts
mixture of myeloblasts and monoblasts/monocytes
monoblasts and or monocytes

32
Q

what are important molecular findings for diagnosis of AML, NOS?

A

FLT3 ITD- it is a negative prognostic factor

Blood and Lymph 3 (5 decks)

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