AML

lecture 2

What is an acute myelogenous leukemia?

a stem cell disorder that has malignant neoplastic proliferation and a maturation block within hematopoietic cells

What populations do we typically see AML in?

elderly and infants

What are the four factors that contribute to AML occurrence?

1. age

2. exposure to chemo, radiation, or benzene

3. myelodysplastic syndromes

4. genetic abnormalities

What symptoms present with AML?

mucus membrane ulcerations

fatigue

anemia

hemorrhage

infections

Which cell population is typically elevated with AML?

WBC

What is the genetic abnormality of CML?

t(9,22)

What is the genetic abnormality of AML-M2?

t(8,21)

What is the genetic abnormality of AML-M3 or APL?

t(15,17)

What is the genetic abnormality of AML-M4?

16q

What is the genetic abnormality of AML-M5?

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

What is the gene product of t(9,22)?

Philadelphia chromosome, or ABL-BCR gene

With the philadelphia chromosome, is prognosis favorable or unfavorable in terms of survival rates?

favorable, survival rate is higher

What are the labs of AML in the peripheral blood?

high WBC counts

>20% blasts

auer rods (characteristic of myelogenous cell lines)

dysplasia of neutrophils

basophilia

What do PLT look like in AML?

giant, hypogranular, low in cell count

What do RBCs look like in AML?

more NRBC, inc. RDW, HJ bodies, basophilic stippling, pappenheimer bodies

What does the bone marrow look like in AML?

hypercellular with lots of blasts, bone destruction, hypercalcemia

What are the subtypes of AML?

AML-M0 to AML-M7

What substance is elevated in basophilic leukemia?

histamine

What is AML-M0?

AML with minimal differentiation

• this means that we have lots of cells that are the same

What cell population is dominant in AML-M0?

blasts that are highly immature and agranular

What is the (1) MPO stain and (2) specific esterase stain reactions in AML-M0?

1. negative

2. negative

What is AML-M1?

AML without maturation

What cell population is dominant in AML-M1?

blasts with auer rods and a tiny bit of granulation

What is the (1) MPO stain and (2) specific esterase stain reactions in AML-M1?

1. weakly positive

2. weakly positive

What is AML-M2?

AML with mautration

What cell population is dominant in AML-M2?

blasts and maturing myeloids → 20 and 10% respectively

auer rods and granules present

What is the (1) MPO stain and (2) specific esterase stain reactions of AML-M2?

1. positive

2. positive

What is AML-M3?

acute promyelocytic leukemia

What two genes are fused in the t(15,17) translocation in AML-M3?

PML → tumor suppressor

RARa → retinoic acid receptor alpha

What is the result of the t(15,17) mutation?

represses genes involved in myeloid maturation

• essentially it blocks myeloid cells from progressing past promyelocyte

What can we use to reverse AML-M3?

ATRA

What are the two forms of AML-M3?

1. hypergranular

2. microgranular

What is the hypergranular form of AML-M3?

hypergranular myeloid cells with auer rod bundles and azurophilic granules that contain procoagulant materials

What condition is associated with AML-M3?

DIC

What is microgranular AML-M3?

myeloid cells with faint granules and tons of WBCs

What is AML-M4?

acute myelomonocytic leukemia → monocyte and granulocyte precursor increase

What cell populations are dominant in AML-M4?

>20% monocyte

>20% neutrophil

plus their precursors

What condition is associated with AML-M4?

leukostasis, or WBC that clog up microvasculature

What are the symptoms of leukostasis?

headache, visual impairment, shortness of breath

• its basically like a big WBC clump that blocks blood flow

What is AML-M5?

acute monocytic/monoblastic leukemia → all the stages of monocytes are here

What are the symptoms of AML-M5?

bleeds, gingival enlargement, CNS involvement

What condition is associated with AML-M5?

leukostasis

What are the two types of AML-M5?

M5a and M5b

What is AML-M5a?

tons of monoblasts in the marrow and the blood

What is AML-M5b?

tons of promonocytes and monocytes in the bone marrow and blood

What do the monocytes look like in AML-M5?

biggie

delicate reticular chromatin

1-2 nucleoli

folded nucleus

phagocytosis of RBC

pseudopodia → cytoplasm appendages

vacuoles

Which AML subtype has a high level of muramidase?

AML-M5

What is AML-M6?

erythroleukemia or Di Guglielmo syndrome

What two cell lines proliferate in AML-M6?

erythroid and granulocyte

What are the symptoms of AML-M6?

bleeds, hepatomegaly, splenomegaly, lymphadenopathy

What happens to the M:E ratio in AML-M6?

decreases to 1:4

What is the AML-M6 variant?

erythremic myelosis → where cell maturation arrests more rapidly of the erythrocyte precursors

• see tons of erythroblasts

AML-M6 can turn into which other subtype of AML?

M1

What do the cells look like in AML-M6?

irregular shaped blasts

irregular nucleoli

multinucleation

cytoplasmic vacuolation

lots of erythroblasts

What is AML-M7?

acute megakaryoblastic leukemia, or acute myelofibrosiis

What cell population is dominant in AML-M7?

megakaryoblasts and megakaryocytes with blebs and reticulin fibrosis

Which two CD markers are positive in AML-M7?

CD41 and CD61

What is the FLT3 mutation?

a gene that codes for a tyrosine kinase, but is now mutated to allow leukomogenesis and spurs AML

If a person has the FLT3 mutation, what is the prognosis?

poor

Which medication can target the FLT3 mutation?

RYDAPT

What two CD markers ID granulocytes?

CD11b and CD33

Which CD markers ID monocytes?

Cd14, CD11b, CD16

What is remission?

the presence of <5% blasts in the marrow and a reduction of immature cells in the periphery

What is the chloroma leukemia?

form of AML that makes tumors of myeloblasts in the tissues

What substance is increased in chloroma? What color does it give off?

MPO increases → green colored tissue

What is eosinophilic leukemia?

a variant of AML or CML that causes immature eosinophils to infiltrate the tissues

What are the symptoms of eosinophilic leukemia?

cardiac failure, coughing, CNS issues

A hypereosinophilic syndrome caused by parasite infection will have what stage of eosinophils?

Mature