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Handout # 1

Leukemia type Pathogenesis Clinical findings Laboratory findings

Acute Myelogenous Leukemia (AML)

Definition: A disorder of stem cell in the bone

marrow.

May involve different myeloid stem cells giving

rise to different types of AML.

For example: it may involve

CFU GEMM --> AML M0

Granulocytic cell --> M1 to M3

CFU GM --> M4

Monocytic stem cell --> M5

Erythroid stem cell --> M6

Megakaryocytic stem cell --> M7

M0 : Minimally differentiated AML

M1 : AML without maturationM2 : AML with maturation

M3 : Acute promyelocytic leukemia ***

M4 : Acute myelomonocytic leukemia

M5 : Acute monocytic leukemia

M6 : Acute erythroleukemia

M7 : Acute megakaryocytic leukemia

Basically a malignant

disorder of Stem cell in

BM

Risk factors:

Irradiation

Benzene

Down syndrome

Most common type of leukemia between 15-39 years of age.

Majority present with bleeding (thrombocytopenia), Fever

(infection),fatigue

andbone pain

.

AML M0 : no Auer rods in myeloblasts; only show positivity for

myeloid CD markers

AML M1: rare Auer Rods present in myeloblasts

AML M3: Most common AML; Auer rods commonly found,

associated with t(8;21) --> better prognosis

AML M3 : Numerous Auer rods and lots of cytoplasmic

granules ; neoplastic cells are promyelocytes (considered as

blasts) ' Most common leukemia associated with DIC;

Characteristic translocation : t(15;17) ; 15 has PML gene, 17

has RAR alpha gene (codes for retinoic acid receptor).Translocations disrupts this. High doses of vitamin A may

induce remission.

AML M4 : presence of both myeloblasts and Monoblasts

AML M5: majprity of cell are monoblasts (positive for non

specific esterase), gum infiltration is characterisitic

AML M6: Erythroblasts and myeloblasts

AML M7: megakaryoblasts

CBC: Normocytic anemia

WBC findings:

Count: 30%

A Typical Myeloblast:

Has large nucleus with few

Contains cytoplasmic granu

Shows presence of Auer rod

Stains positive for MPO andStains Negativly for TdT and

CD markers:

Positive for myeloid mark

Negative for CD 10, 19,2

markers)

Acute Lymphoblastic leukemia (ALL)Definition: Stem cell disorder arising from

lymphoid stem cells

Classification:

FAB classification:

L1:

L2:

L3: leukemic form of Burkitt's lymphoma

Immunological classification:

B-ALL

Early pre B : CALLA ag positive; MC typePre B

Mature B

T-ALL : Tdt positive

Disorder of Lymphoidstem cells

ALL is most common leukemia and overall cancer inchildren.

Most children

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Handout # 2

Definition Pathogenesis Clinical findingsChronic Myeloid Leukemia

(CML)

Definition: neoplastic

proliferation of pluripotent

stem cell. With predominant

involvement of granulocytic

series of cells.

Risk factors:

Radiation (1945 atomic bomb)

Benzene

Chromosome abnormality:

t(9;22)

Translocation ofabl from 9 to

22 with fusion at break pointcluster region (bcr)

Formation ofbcr-abl fusion

gene --> tyrosine kinase activity

Chromosome 22 is called

Philadelphia chromosome

Common leukemia between 40-60 years of age.

Signs of anemia: malaise, fatigue

Hypermetabolic state: associated with

hyperuricemia, fever, weight loss and sweating.

Massive splenomegaly : Dragging sensation in

abdomen ; Hepatomegaly

Soft tissue collections of leukemic cells: calledchloromas

Chronic lymphocytic

leukemia (CLL):

Most commonly arises from

virgin B cells.

Neoplastic disorder of virign B

cells (cannot differentiate into

plasma cells -->

hypogammaglobulinemia

Most common overall leukemia

Most common leukemia in patients over 60

years.

MC cause ofgeneralized nonpainful

lymphadenopathy in an elderly patient.

25% asymptomatic at presentation

Generalized nonpainful lymphadenopathy

Hepatosplenomegaly

Increased incidence ofautoimmune hemolytic

anemia, autoimmune thrombocytopenia,

hypogammaglobulinemia

Adult T cell leukemia(ATCL)

Definition: malignant T cell

leukemia associated with

HTLV-1 infection

Most common in Japan and CaribbeanGeneralized lymphadenopathy

Hepatosplenomegaly

Skin infiltration

Lytic lesion in bone --> hypercalcemia

Hairy cell leukemia (HCL)

Malignancy of B cells

Most common in middle agen men

Splenomegaly is the most common physical

finding

Lymphadenopathy is absent

Increased incidence of Mycobacterium aviumintracellulare

Chronic leukemias

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Handout # 2

Laboratory findingsNormocytic normochromic anemia

WBC findings: Marked increase in count (50,000

to 200,000)

Mature and immature WBCs (myelocyte most

abundant cell)

Increased basophils and eosinophi.

Myeloblast: less than 10% of total cellsPlatelets: thrombocytosis / thrombocytopenia

(50/50)

Bone marrow: hypercellular, increased M/E ratio,

fibrosis common in late stages

Chromosome studies: Philadelphia

chromosome (positive in 95% cases), bcr-abl

fusion gene (positive in 100% cases)

LAP score: low

WBC findings: absolute lymphocytosis (15,000 -

200,000) with smudge cells (fragile lymphoid

cells).

Platelets: thrombocytopenia

Bone marrow: infiltrated by neoplastic lymphoid

cells

Miscellaneous: hypogammaglobulinemia

Lymphoblast with T cell marker. Tumor cells haveflower shaped or 4 clover leaf shaped nucleus

Pancytopenia is characteristic

WBC findings: malignant B cells with hairy

projections.

Positive Tartrate resistant acid phosphatase

stain (TRAP stain)Bone marrow: packed with malignat cells that

resemble fried eggs, with ample cytoplasm and

small nucleus (yolk).