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
  1. DNA alkylating agents

2. topoisomerase-II

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4
Q

What are the biggest risk factors for acute leukemia?

A
  1. previous chemotherapy (especially DNA alkylating agents and topoisomerase-II)
  2. 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

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

CD34- a marker of immaturity also expressed in myeloblasts

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7
Q

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

A

CD19 and CD22 but NOT CD20

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8
Q

What 3 cytogenetic findings can occur with B-ALL?

A
  • t(9;22) aka Ph +
  • translocation of 11q23
  • t(12;21)
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9
Q

How is the t(9;22) 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? Worst prognosis?

A

t(12;21)-best
T (9;22)- worst

  • think of 9;22 being worse than 911
    • Think of B-ALL as affecting mostly BABIES
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11
Q

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

A

T-ALL often presents with a component of T-LBL (lymphoblastic lymphoma). In TLBL the T cells hang out in the Thymus and a mass develops.

Most common in Teenagers. Remember T-ALL=Thymus + Teenagers

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12
Q

T-ALL/T-LBL favors what gender and age group?

A

Teenage Males

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13
Q

What markers are seen in cells with T-ALL?

A

-CD2, CD3, and/or CD7 (most important)

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14
Q

ALL has the worst prognosis for what age group?

A

Adults and adolescents, even though affects mostly kids under 6.

*ALL kills Adults and Adolescents (A’s).

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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

Neoplastic accumulation of myeloblasts (>20%) in bone marrow.

*Exceptions to this rule only in the presence of specific cytogenetic findings.

17
Q

An Auer Rod identifies a cell as what kind?

A

Myeloblast.

An Auer rod is a crystal aggregates of MPO.
MPO is characteristic of Myeloblasts.

18
Q

What markers are typically seen in myeloblasts?

A

Myeloperoxidase (MPO)- Most important

CD117 (also called C-kit)

19
Q

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

A

Blasts

20
Q

There are five kinds of AML, what are they?

A
  1. t(8;21) RUNX1 “alpha core binding factor”
  2. inv(16) or t(16;16) “baso eos” (beta core binding factor)
  3. (15;17) PML-RARA (APL) **most important
  4. t(1;22) associated with downs
  5. abnormalities with 11q23 of MLL gene
21
Q

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

A

RUNX1 encodes alpha unit of core binding factor (CBF), which is needed for differentiation.

22
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. See abnormal “baso-eos”

23
Q

What is APL? how does it work?

A
  • A subtype of AML (acute promyelocytic leukemia).
  • Promyelocytes predominate instead of blasts because no RARA is produced.
  • t(15;17)
  • Typical morphology is FAGGOT CELLS! Many Auer rods.
24
Q

How can you treat patients with APL?

A

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

NO CHEMO NECESSARY!

25
Q

Some cases of APL can lead to what blood complication?

A

DIC- Disseminated intravascular coagulation

This is why it is important to know if an acute leukemia is APL. You can be aware of the DIC possibility

26
Q

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

A

Down syndrome
Megakaryoblastic

t(1;22) is also known as Acute Megakaryoblastic Leukemia

27
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.

28
Q

Problems in this tissue arise in patients with Acute Monocytic Leukemia.

A

What are the gums?

29
Q

Which cell lineage expresses TdT?

A

Lymphoblasts

The broncos LBs scored TDs ALL day
LBs=Lymphoblasts
TDs=TdT marker
ALL= ALL- most prominent leukemia

30
Q

What evidence exists for “leukemic stem cells”?

A

Tumor relapses after chemo resulted in homogenous CD34+/CD38- cells. Since heterogeneity is found in most cancer metastases, it reinforces that LSCs exist

31
Q

Explain why patients with leukemia may exhibit fatigue, bruising, hemorrhage, and frequent infection.

A

Leukemias cause “crowding out” of other blood cells in the bone marrow.

Fatigue- Anemia due to dec. RBC
Bruising, hemorrhage- Thrmobocytopenia
Frequent infection- Neutropenia

32
Q

What is the genetic marker of immaturity in Leukemia?

A

CD34

33
Q

What are the 5 factors affecting prognosis of ALL?

What combination of these factors would give the BEST prognosis.

A
  1. Age - 1-10
  2. WBC count- Low WBC
  3. Response to therapy- Fast or normal response
  4. # of chromosomes- Hyperdiploidy (51-65)
  5. B vs T lineage - B-ALL
34
Q

List 3 molecular markers currently used to predict prognosis in patients with AML with normal karyotype. Which one of these is the “trump” for prognosis?

A

FLT3- Poor prognosis
NPM-1 Good prognosis
CEBPA- GOod prognosis

Just remember FLT3, it is the trump and the only negative indicator