This document discusses various types of leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). It covers classification systems for leukemia such as the French-American-British (FAB) and World Health Organization (WHO) classifications. Key diagnostic tests are outlined including cytochemical staining reactions, immunophenotyping using cell surface markers, cytogenetics including karyotyping, and molecular testing. Signs, symptoms and laboratory findings for different types of leukemia are also summarized.

1. Week 10: Leukemia
 AML
 ALL
 FAB classification
 WHO classification
 Cytochemistries
 MPO
 SBB
 PAS
 ORO
 CD markers
 Flowcytometry
 CML
 CLL
 Karyotype
 Ph chromosome
 LAP

2. Signs and Symptoms of AML
 Insidious nonspecific onset
 Pallor due to anemia
 Febrile due to ineffective WBC
 Petechiae due to thrombocytopenia
 Mucus membrane and gum bleed in
M4 and M5
 Bone pain

3. Typical Labs
of AML
 Leukocytosis
 Blastemia
 Leukemic hiatus
 Auer rods in M2, M3,
M4
 Thrombocytopenia
 Anemia
 >20% blasts in BM

4. Other Findings
 CD 13 and CD 33 in flowcytometry
 Cytochemistries
 Myeloperoxidase
 Sudan black B
 Choloroacetate esterase (specific)
 Nonspecific esterase

5. FAB (1976) Classification
 M0 -- Undifferentiated AML
 M1 -- AML without maturation
 M2 -- AML with maturation
 M3 -- Acute Promyelocytic Leukemia
 M4 -- Acute Meylomonocytic Leukemia
 M5 -- Acute Monocytic Leukemia
 M6 -- Erythroleukemia (DiGuglielmo’s)
 M7 -- Megakaryoblastic Leukemia

7. M1 and M2

10. Myeloperoxidase
(MPO)
p-Phenylene diamine + Catecol + H2O2
MPO > Brown black deposits

11. M3
M5
M4

12. Chloracetate (Specific) Esterase
Myeloid Cell Line
Naphthol-ASD-chloracetate
CAE > Free naphthol compounds
+ Stable diazonium salt (eg, Fast Corinth)
> Red deposit

13. Non-Specific Esterase
Monocytic Line
 Naphthyl acetate
ANAE > Free naphthyl compounds
+Stable diazonium salt (eg, Fast blue RR)
> Brown deposits

14. Double Esterase in M4
NSE with Fl inhibition
Histiocyte

15. FAB vs WHO Classifications of
Hematologic Neoplasm
 FAB criteria
 Morphology
 Cytochemistry
 WHO criteria
 Morphology
 Immunophenotyping
 Genetic features
 Karyotyping
 Molecular testing
 Clinical features

16. WHO Classification of AML
 AML with recurrent cytogenic
translocations
 AML with multi-lineage dysplasia
 AML and myelodysplasia, therapy related
 AML, not otherwise categorized

17. AML with Recurrent Cytogenetic
Translocations (WHO 1995)
 t(8;21) -- some maturation of neutrophilic line;
rare in older patients; AML1/ETO fusion protein;
>90% FAB M2
 t(15;17) -- APL (granular and microgranular
variants); retinoic acid receptor (RAR) leukemias;
middle aged adults; DIC
 inv(16) or t(16;16) -- monocytic and granulocytic;
abnormal eosinophilic component
 11q23 -- monocytic; children; most common is
t(9;11)

19. FAB Classification of ALL
 L1: Small homogeneous blasts; mostly in
children
 L2: Large heterogeneous blasts; mostly in
adults
 L3: “Burkitt” large basophilic B-cell blasts
with vacuoles

20. L3
L2

21. Periodic Acid Schiff
Periodic acid + Glycogen
oxidation > Aldehyde + Schiff reagent
(para-rosaniline, Na metabisulfite)
> Red deposit

22. ALL Cytochemistries
 Oil Red O: stains L3 vacuoles
 Terminal deoxynucleotidyl transferase
(Tdt): DNA polymerase in early
lymphoblasts
 Cell surface markers (CD’s)
 Cytoplasmic and surface immunoglobulins:
B-cell line
 T-cell receptor (TCR)

23. WHO Classification of
Lymphoproliferative Syndromes
 Precursor B Lymphoblastic Leukemia/Lymphoma
(ALL/LBL) -- ALL in children (80-85% of
childhood ALL); LBL in young adults and rare;
FAB L1 or L2 blast morphology
 Precursor T ALL/LBL -- 15% of childhood ALL
and 25% of adult ALL
 Burkitt Leukemia/Lymphoma (FAB L3)

24. •Antigens •B-Lineage •T-Lineage
•HLA Dr
•Tdt
•CD34
•+
•+
•+
•0 to +
•+
•0
•CD19
•C 22
•CD10
•CD20
•Cyt-
•SIg
•+
•cALL and older
•cALL and older
•Pre-B and older
•Pre-B and older
•B-ALL
•Pre-T
•Pre-T
•Pre-T
•0
•0
•0
•CD7
•CD3
•CD5
•CD2
•CD1
•0
•0
•0
•0
•0
•+
•+
•+
•T-ALL
•T-ALL

25. Indicators Favorable Poor
WBC < 50,000/L  50,000/L
Age 1 - 10 < 1 or 10
Gender Female Male
Blast B-cell T-cell and mixed
Karyotype Hyperploidy
Trisomy 4, 10, 17
t(12;21) (TEL/AML1)
Hypoploidy
Trisomy 5
t(1;19 (E2A/PBX1)
Mixed lineage leukemia
T(9;22) (Ph)
BM blast count
during induction
Mkd reduction at day 7 Mild reduction at day 7
Prognosis

26. FAB (1982) Classification of
Myeloproliferative Disease (MPD)
 Chronic Myelocytic Leukemia (CML)
 Polycythemia Vera (PV)
 Essential Thrombocythemia (ET)
 Agnogenic Myeloid Metaplasia with or without
Myelofibrosis (AMM)
 Benign Leukemoid Reaction

27. WHO Classification of MPS
(1997)
 CML becomes
 CML, Ph + t(9;22) BCR/ABL
 Chronic Neutrophilic Leukemia (CNL)
 Chronic Eosinophilic Leukemia and Hyper-
eosinophilic Syndrome (CEL/HES)
 PV remains PV
 ET remains ET
 AMM becomes
 Chronic Idiopathic Myelofibrosis

28. Myelofibrosis

29. Myelofibrosis

31. Chronic Lymphocytic Leukemia
 Exclusive in elderly
 Lyphocytosis unrelated to viral infection
 Hyper-mature lymphocytes with highly
condensed nuclei
 Smudge cells: preventable with a drop of
bovine albumin

32. CLL
PB and BM

36. WHO Lymphoid Neoplasms
 B cell neoplasms
 T/NK cell neoplasms
 Hodgkin lymphoma (disease)

37. Mature B Cell Neoplasms
 B cell CLL/SLL
 B prolymphocytic
leukemia
 Burkitt’s lymphoma /
leukemia
 Splenic marginal zone
B lymphoma
 Extranodal marginal B
lymphoma
 Hairy cell leukemia
 Lymphoplasmocytic
leukemia
 Mantle cell lymphoma
 Plasma cell myeloma /
plasmacytoma
 Follicular lymphoma
 Diffuse large B
lymphoma

38. T/NK Cell Neoplasms
 T prolymphocytic
leukemia
 T granular
lymphocytic leukemia
 Aggressive NK cell
leukemia
 Adult T lymphoma /
leukemia
 Mycosis fungoides
(Sezary syndrome)
 Anaplastic large cell
lymphoma
 Hepatosplenic T
lymphoma
 Peripheral T lymphoma
 Immunoblastic T
lymphoma