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Heme > Heme Malignancies 2: Arising in the Bone Marrow > Flashcards

Heme Malignancies 2: Arising in the Bone Marrow Flashcards

1
Q

What is the defining feature of Acute leukemias?

A

Blasts

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2
Q

Immunophenotype of blasts, in general.

A

CD34+

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3
Q

Immunophenotype of MYELOID BLASTS

A

CD34+, CD33+

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4
Q

Immunophenotype of LYMPHOID BLASTS

A

Tdt+, CD10+

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5
Q

Immuniphenotype seen in Lymphomas.

A

Mostly B cells are lymphomas. so CD19+ and CD20+

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6
Q

Can you diagnose a cancer on immunophenotype alone?

A

NO! But it is an essential part of the diagnostic workup.

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7
Q

What are the 4 subtypes of AML?

A
  1. AML with no cytogenetic findings
  2. AML - RUNX1-RUNX1
  3. Acute Premyelocytic Leukemia - PML-RARA
  4. Acute Myelomonocytic Leukemia - CBFC-MYH11
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8
Q

What is the translocation associated with Acute Premyelocytic Leukemia?

A

t(15,17)

PML-RARA

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9
Q

What is the translocation associated with AML (normal with cytogenetics)

A

RUNX1-RUNX1

t(8;21)

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10
Q

What cytogenetic finding is associated with Acute Myelomonocytic Leukemia? (AML subtype)

A

CBFC-MYH11

inv (16,16)

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11
Q

Can you diagnose the 3 subtypes of AML with no cytogenetic findings if the blast count is below 20%?

A

Damn right, and you better catch it quick.

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12
Q

Talk about AML with the PML-RARA TF translocation.

A

t(15;17)
Acute Promyelocytic Leukemia

PML - TF
RARA- TF (retinoid acid receptor alpha)

Inhibits granulocyte differentiation.

Treat with ATRA - All-Trans Retinoic Acid.
Induced differentiation of blasts to granulocytes.

Induces clinical remission.

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13
Q

Immunophenotype of AML with PML-RARA translocation.

A

CD34 (-) ….weird.

CD-13+, CD33+ (immature myelocytes)

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14
Q

What is the translocation number of AML with RUNX1-RUNX1T1 fusion protein?

A

t(8;21)

Rhymes. Run Run 8;21.

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15
Q

What is the immunophenotype of AML with CBFC-MYH11 translocation?

A

CD14+ CD11b+ (MONOCYTES)

CD13+,CD33+ (Granulocytes)

CD34+ (blasts)

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16
Q

Immunophenotype of AML with normal cytogenetics.

A

CD33+, CD34+ (blasts)

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17
Q

What is different about the treatment of AML with normal cytogenetics (compared to the subtypes with cytogeneti anomalies)?

A

How they are treated depends on the result of targeted DNA sequencing studies

18
Q

What is the prognosis for AML with a complex karyotype?

A

Cases with 3 or more cytogenetic findings (translocations, trisomies, monosomies) have a POOR PROGNOSIS.

19
Q

What does ALL stand for?

A

Acute Lymphoblastic Leukemia

20
Q

In what age group do you see the most ALL?

A

75% of ALL cases occur in KIDS UNDER 6 AND over 80% of acute leukemias in kids are ALL.

~80% cure rate in kids, ~50% in adults

See “kids under 6” think ALL.

21
Q

What % of the marrow must be blasts for an ALL diagnosis?

22
Q

A child has ALL with a t(9;22) translocation. What is that translocation? What other cancer is this translocation also found in? What’s the difference?

A

ALL t(9;22) is the BCR-ABL fusion protein.

The 9:22 translocation is also in CML, but the fusion protein is DIFFERENT because the breaks occur at different points, creating a variant of BCR-ABL.

23
Q

How can you distinguish a type of AML from ALL if you can only run one test to differentiate?

A

Run a flow cytometric analysis.

The AML markers are CD34+ (blast) and CD33+ (granulocyte).

The ALLs are TdT+, whether they are B or T cell lymphomas.

24
Q

For the following subtypes of B-cell ALL, say whether the prognosis is good or bad.

  1. BCR-ABL
  2. (11;19) MLL rearranged
  3. t(12;21) TEL-AML1(ETV6-RUNX1)
  4. Hyperdiploid (>50 chromosomes)
A
  1. t(9;22) BCR-ABL = bad prognosis
  2. t(11;19) MLL rearranged = bad prognosis
  3. t(12;21) TEL-AML1 (ETV6-RUNX1) = good prognosis
  4. Hyperdiploid (>50 chromocomes) = good prognosis.
25
What is the ALL t(9;22) BCR-ABL immunophenotype?
CD10+ (germinal center) CD19+ (B-cell) Tdt + (lymphocyte)
26
What's the ALL t(11;19) MLL rearranged immuniphenotype?
CD10 - (how you tell it from bcr-abl ALL) CD19+ (B-cell) TdT+
27
What's the immunophenotype of ALL with t(12;21) ? | Weird one
Good prognosis TdT+ CD34+ (blast) CD10+ CD20-
28
What's the immunophentype of T-ALL? (T-cell ALL)
TdT+ CD3+ CD5+
29
How do kids with T-ALL present in the clinic?
Thymic masses, lymph node masses, splenomegaly.
30
What is the general translocation principle for T-ALL?
T-cell Acute Lymphoblastic Leukemia always has an oncogene translocated to an Ig or TCR promotor in Ch 14.
31
And now we move on to MYELOPROLIFERATIVE DISEASES:
yes
32
What is a Myeloproliferative disorder?
Myeloproliferative disorders are a group of conditions that cause blood cells -- platelets, white blood cells, and red blood cells -- to grow abnormally in the bone marrow.
33
Name the relevant Myeloproliferative Disorders.
CML Mastocytosis Primary Myelofibrosis Polycythemia Vera Essential Thrombocytopenia
34
How can you tell an infection apart from a myeloproliferative disorder?
In infections, bands will outnumber myelocytes and metamyelocytes. The opposite will occur in a myeloproliferative disorder. Also, toxic granulation in neutrophils will be seen during an INFECTION. Not in a neoplasm.
35
What's the abnormal chromosome in CML called? What's the translocation? Fusion protein product? Treatment?
Philadelphia chromosome t(9;22) - constitutive tyrosine kinase activity BCR-ABL fusion protein Treat with Imatinib
36
What is the prognosis for CML?
GOOD! 90% cure rate
37
You suspect a man has either sepsis or a myeloproliferative disorder. You run a CBC and manual diff, and suspect CML. What test do you do to confirm?
RT-PCR of peripheral blood for BCR-ABL fusion protein
38
If untreated, what can CML turn into?
Acute leukemia, myeloid OR lymphoid.
39
What myeloproliferative disease results in an increase in red cell count?
Polycythemia Vera
40
What is the mutation in 95% of Polycythemia Vera cases?
Jak2 mutation. Active Epo receptor even in absence of erythropoietin.
41
What things do you look for to diagnose polycythema vera?
CBC: increased RBC ct. and Hct. Labs: Decreased Epo production (not needed) Morphology: Erythroid hyperplasia in the bone marrow and Increased RBCs on smear.
42
Stopped at Essential Thrombocythemia
yes

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