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Pathophysiology - Hematology > Acute Leukemias > Flashcards

Acute Leukemias Flashcards

1
Q

What are general features of acute leukemias?

A

Unregulated proliferation of blast cells in the bone marrow (>20%) leading to inhibition of normal hematopoiesis

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2
Q

What do leukemias typically look like in the peripheral blood?

A

Blasts enter the bloodstream, resulting in a high WBC count. They are large, immature clonal cells with punched out nucleoli.

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3
Q

How does inhibition of normal hematopoiesis explain the classic signs of acute leukemias?

A

Anemia -> fatigue, pallor
Thrombocytopenia -> bleeding (ecchymosis, epistaxis, menorrhagia, petechiae)
Neutropenia -> infections

Fever / bone pain from crowding out of bone marrow by blast cells

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4
Q

What is the most common acute leukemia in adults and what are the risk factors?

A

Acute myeloid leukemia (AML)

  • Down syndrome
  • Radiation and alkylating chemotherapy
  • Myeloproliferative disorders
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5
Q

What is a myeloid sarcoma and give one example of a manifestation of it?

A

Solid tumor of leukemic myeloid cells occurring outside the bone marrow

  • > sometimes a presentation of AML
  • > common in skin, heart, testes, and brain
  • > Leukemia cutis - when myeloid blast cells infiltrate the tissues
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6
Q

What tissue infiltration is characteristic of acute monocytic leukemia?

A

Gingival hypertrophy -> monoblasts have a tropism for the gums

Keep in mind this is a type of AML

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7
Q

What is APL, what mutation is associated with it, and what is the mechanism?

A

Acute Promyelocytic Leukemia
-> associated with t(15;17) translocation, where RAR receptor on chromosome 17 is disrupted by PML gene, blocking promyelocyte differentiation

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8
Q

What leukemias are associated with Down syndrome and at what ages?

A

Before age 5: Acute megakaryoblastic anemia (type of AML)

After age 5: Acute lymphoblastic leukemia (ALL)

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9
Q

How do the blasts look in AML on peripheral smear?

A

immature cells with large nuclei, prominent (punched out) nucleoli, fine granular chromatin, pale blue cytoplasm, and granules

with a pathognomonic finding

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10
Q

What finding is pathognomonic of AML? What are they?

A

Auer Rods in the cytoplasm of blast cells

They are crystal aggregates of myeloperoxidase (MPO)

For this reason these cells are MPO+

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11
Q

What type of AML sees the most Auer rods?

A

Acute Promyelocytic Leukemia -> differentiating into neutrophils so they will have the most MPO

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12
Q

How does leukemic vs normal bone marrow look different in general?

A

In normal bone marrow, cell populations are very diverse

In leukemia - there will be clonal proliferations of blast cells crowding out diversity

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13
Q

Other than myeloperoxidase staining, give two other stains used to differentiate AML from ALL.

A
  1. Sudan Black stain - only stains myeloblasts but not lymphoblasts
  2. Non-specific esterase - identifies cells of monocyte origin
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14
Q

What are the myeloid markers by flow cytometry?

A

CD13, CD33

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15
Q

What are the monocyte markers for flow cytometry?

A

CD11 (integrin receptors for ICAM binding)

CD14 (TLR4)

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16
Q

What is the immature hematopoietic stem cell marker? If it’s a lymphoid cell specifically?

A

CD34

Specifically lymphoid cells:
TdT = special DNA prolymerase
-> only seen in lymphoBLASTS, not mature lymphocytes

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17
Q

What are the flow cytometry markers for B-cell ALL?

A

CD10
CD19
CD20
CD22

18
Q

What are the flow cytometry markers for T cell ALL?

A

CD2, CD3, CD7 (numbers 2-8, will NOT express CD10)

19
Q

Are cytogenetic changes associated with AML?

A

Yes, greater than 50% of patients have abnormal karyotypes of some kind on analysis of metaphase-dividing cells

-> i.e. Philadelphia chromosome, preceded by CML

20
Q

When in the cell cycle does FISH identify abnormalities? What abnormalities can you find?

A

In the interphase / nondividing cells

Can see microdeletions, translocations (i.e. philadelphia chromosomes), and duplications

21
Q

What genetic analysis is done on leukemic cells and why? Which AML has the worst prognosis? Best?

A

Whole genome molecular marker analysis

Worst: FLT-3+ (FMS-related tyrosine kinase)
Best: NPM1+, CEBPA+

NPM: Nucleophosphomin

22
Q

What are the three AML’s which do NOT require >20% blasts in bone marrow to diagnose them as AML (this is unique)? What is wrong in the first two of them?

A

First two are related to dysfunction in core binding factors (CBF) which are essential for normal hematopoesis

  1. t(8;21) - RUNX1 - remember one less than 9;22
  2. inversion (16)
  3. t(15;17) - RAR dysfunction promyelocytic leukemia
23
Q

How do you recognize APL and why is it important to recognize it early? What do RBCs look like in it?

A

Cells are distinctive because of many cytoplasmic granules and stacks of Auer rods (MPO+)

Recognize early because when cells are lysed, MPO activates coagulation cascade, causing a procoagulant state

DIC is a common presentation in these patients

RBCs - schistocytes due to microangiopathic cleavage

24
Q

What is the treatment for APL?

A

All-trans retinoic acid (Atra)

-> induces differentiation of promyelocytes

25
Q

In general, what patients have good prognosis vs high risk?

A

Good risk:
t(8;21), inv16, t(15;17), or normal cytogenetics with FLT-3 wild type

High risk: del(5) MDS progression, FTL-3 positve, multiple cytogenetic abnormalities

26
Q

How do we treat fit patients with good risk?

A

Induction - standard chemotherapy regimen of 7 days Ara-C + 3 days athracycline

Consolidation with 3-4 cycles of high dose Ara-C

27
Q

How do we treat fit patients with medium / high risk vs non-fit patients?

A

Fit patients with medium/high risk = might do some chemotherapy, but probably go right to bone marrow transplant

Non-fit (older) - supportive care, hypomethylating agents to slow progression of disease

28
Q

How does an ALL differ from a lymphoma?

A

If lymphoblasts are mostly confined to bone marrow / leukemic phase it is an ALL.

If lymphoblasts are mostly confined to lymph nodes it is a lymphoma

29
Q

What age group tends to get ALL, and is normally B or T cell ALL?

A

ALL is the most common cancer in children

85% of ALL is of B cell origin

30
Q

In what way are AML and ALL presentations similar?

A

Similarities: Anemia thrombocytopenia and neutropenia give classic AML presentation of nonspecific symptoms due to lymphoblasts crowding out normal hematopoiesis, causing cytopenias

31
Q

How can symptoms of ALL be told apart from AML?

A

Testicular swelling (scrotal involvement) is very common

CNS involvement much more common than AML

Hepatomegaly, splenomegaly, and lymphadenopathy much more common than AML

32
Q

What will PAS stain show for ALL? How does the nucleus of the lymphoblasts generally appear in ALL?

A

PAS - dot-like positive staining encircling nucleus

Nucleus has folds or grooves in them

33
Q

What is TdT?

A

Terminal deoxynucleotidyl transferase

-> a DNA polymerase marker specific to immature lymphoblasts for both T and B cells

34
Q

Who tends to get the t(9;22) ALL? What’s the prognosis?

A

Mostly adults

  • > progression from CML with 210 kD protein
  • > de novo ALL mutation with 190 kD protein

Because its in adults, prognosis is poor

35
Q

Are hyperdiploidy and hypodiploidy good or poor prognostic factors in ALL?

A

Hyperdiploidy - good prognosis - 51-65 chromosomes

hypodiploidy - poor prognosis (these strong cells are able to live without enough genes!) - <45 chromosomes

36
Q

What ALL is most commonly seen in children and has a good prognosis?

A

t(12;21) - B cell leukemia

37
Q

What causes Burkitt lymphoma/Leukemia overlaps?

A

Translocation of c-myc gene from chromosome 8 to another constitutively active site (usually chromosome 14 where the Ig heavy chain locus is)

Ig heavy chain locus constitutively expressed in B cells
-> t(8;14) causes Burkitt lymphoma due to overexpression of c-myc

Associated with EBV

38
Q

How does the bone marrow appear in Burkitt lymphoma / leukemia and why?

A

Starry sky appearance

Night background = basophilic appearance of sheets of B cells interspersed with “tingible body” macrophages which are the dying B cells due to high mitotic rate

39
Q

How does T-cell ALL present?

A

TTT
T-cell
Thymic mass
Teenager

Presents as mediastinal mass in adolescence, associated with lymphadenopathy

40
Q

How does treatment of ALL differ from AML?

A

Although the response to chemotherapy is excellent, ALL generally requires prophylaxis to the scrotum and CSF
-> cannot pass these blood barriers without direct injection of chemo (i.e. intrathecal)

41
Q

What cell type is CD43 a marker of?

A

T cell

Pathophysiology - Hematology (14 decks)

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