Acute Myelogenous Disorders

What are stem cell disorders characterized by?

What are stem cell disorders characterized by?

- malignant neoplastic proliferation
- maturation block and accumulation of immature cells

Acute leukemias are more ________ and have ________ onset in their clinical course

refractory to treatment, rapid onset

AML is associated with?

- age (median 65)
- exposure (chemo, benzene)
- MDS
- genetic abnormalities

What are the symptoms of AML?

mucous membrane ulcerations, anemia, hemorrhage, infection, HIGH WBCs, resistant to chemo

Peripheral blood findings for AML

- blasts >20% with auer rods
- dysplastic neutrophils
- basophilia
- RBC inclusions, inc RDW, plt abnormalities

Bone marrow in AML

hypercellular, lots of blasts (critical to evaluate for AML)

Bone destruction in AML leads to?

hypercalcemia

What are the classifications of AML based on? (FAB corp)

morphology and cytochemical staining of cells

AML subgroups 1-6 (long sorry)

1. AML w/ recurrent genetic abnormos
2. AML w/ myelodysplasia changes
3. therapy related
4. AML not specified
5. myeloid sarcoma
6. related to Down Syndrome

M0 (AML w/ minimal differentiation)

agranular cytoplasm, MPO =, specific esterase =, CD34 +
5% of AML cases

M1 (AML w/o maturation)

- adults
- 90% of blasts show no maturation
- auer rods and/or granules (3% blasts MPO and specific +)

M2 (AML with maturation)

- 20% blasts (10% maturing)
- auer rods and/or granules (MPO and specific +)
- responds to treatment

What is the translocation associated with M2?

t(8;21)

APL (acute promyelocytic leukemia) translocation and common presentation

- DIC
- t(15;17)

What does t(15;17) do?

fuses PML (tumor supressor) and RARa, promotes transcription repression of genes in myeloid terminal (block of differentiation)

How would you treat APL with a t(15;17) translocation?

ATRA (all-trans retinoic acid)

Hypergranular APL

auer rod bundles, azurophilic granules, worse DIC, WBCs not as elevated

Microgranular APL

- faint granules
- 20-30% of APL
- ^^^WBC

M4: Acute Myelomonocytic Leukemia (AMML)

- lots of mono and granulocyte precursors (>20%)
- 16q mutation
- high risk of leukostasis

leukostasis

- dilated thin walled blood vessels w/ monos
- brain and lung involvement
- headache, visual impairment, SOB

M5 a and b (acute monocytic/monoblastic leukemia)

- lots of monoblasts, promonos, and monos
- bleeding, gingival enlargement, CNS involvement
- high risk of leukostasis
- resistant to treatment

What translocations are associated with M5 a and b?

t(9;11), t(8;16)

AML-M5a

poorly differentiated, large blasts in BM and blood

AML-M5b

differentiated, monos and promonos in BM and blood (most common is promono)

AML-M5 promonocyte characteristics

- phagocytosis of RBCs or cell debris
- pseudopodia w/ basophilic cytoplasm
- ^^^ muramidase in serum/urine

M6 (erythroleukemia)

- Di Guglielmo syndrome
- abnormal prolif of erythroid and granulocytic precursors
- bleeding, hepato/splenomegaly, lymphadenopathy
- DEC M:E ratio (1:2-4)

Erythremic myelosis

variant of M6 w/ more rapid course and an arrest in maturation of erythrocytic precursors (erythroblastic w/o maturation)

M6 can terminate in:

AML-M1

M7 (acute megakaryoblastic leukemia)

- 50%/more megas in marrow
- inc in reticulin fibrosis
- cytoplasmic blebs
- most rare (3-5% of leukemias)

What CD markers are present in AML-M7?

CD41 and CD61

FLT3 mutation

- type 3 receptor tyrosine kinase
- lekomogenesis from activated TK
- 30% of total AML cases

What is the target therapy for FLT3 mutation?

RYDAPT (inhibits FLT3 signaling and cell prolif)

CBF gene complex

transcription factor complex (better prognosis)

Granulocyte precursor identifiers for flow

CD11b and CD33

monocytic precursor identifiers for flow

CD14, CD11b, CD16

remission

presence of fewer than 5% blasts in the marrow w/ a reduction of immature cells in the peripheral blood

What is the only "cure" for AML?

stem cell transplant

Chloroma

- tumors of myeloblasts in tissues
- high MPO conc. (green appearance)

Basophilic leukemia

- inc in blood histamine
- rarest form of all leukemias

Myeloblastic Sarcoma

- tumors of myeloblasts in tissues
- absence of MPO pigment (different from chloroma)

Eosinophilic Leukemia

- eos infiltrate tissues
- chronic cough, cardiac failure, CNS involvement
- other myeloid precursors involved