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AML ORO
ALL CD markers
FAB classification Flowcytometry
WHO classification CML
Cytochemistries CLL
MPO Karyotype
SBB Ph chromosome
PAS LAP
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
Typical Labs
of AML
Leukocytosis
Blastemia
Leukemic hiatus
Auer rods in M2, M3,
M4
Thrombocytopenia
Anemia
>20% blasts in BM
Other Findings
CD 13 and CD 33 in flowcytometry
Cytochemistries
Myeloperoxidase
Sudan black B
Nonspecific esterase
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
M1 and M2
Myeloperoxidase
(MPO)
M5
Chloracetate (Specific) Esterase
Naphthol-ASD-chloracetate
CAE > Free naphthol compounds
Monocytic Line
Naphthyl acetate
ANAE > Free naphthyl compounds
Karyotyping
Molecular testing
Clinical features
WHO Classification of AML
AML with recurrent cytogenic
translocations
AML with multi-lineage dysplasia
AML and myelodysplasia, therapy related
AML, not otherwise categorized
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)
FAB Classification of ALL
(para-rosaniline, Na metabisulfite)
> Red deposit
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)
WHO Classification of
Lymphoproliferative Syndromes
•CD19 •+ •Pre-T
•C 22 •cALL and older •Pre-T
•CD10 •cALL and older •Pre-T
•CD20 •Pre-B and older •0
•Cyt- •Pre-B and older •0
•SIg •B-ALL •0
•CD7 •0 •+
•CD3 •0 •+
•CD5 •0 •+
•CD2 •0 •T-ALL
•CD1 •0 •T-ALL
Prognosis
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 Hypoploidy
Trisomy 4, 10, 17 Trisomy 5
t(12;21) (TEL/AML1) t(1;19 (E2A/PBX1)
Mixed lineage leukemia
T(9;22) (Ph)
2+ 3+ 4+
LAP Score
Example:
0 x 35 cells = 0
1+ x 30 cells = 30
2+ x 20 cells = 40
3+ x 10 cells = 30
4+ x 5 cells = 20
120 LAP Score
Philadelphia Chromosome
9 and 22 translocation almost specific to CML
Karyotype to visualize Ph chromosome
Produces BCR/c-abl fusion oncogene
Gene product p190 is a hyperactive tyrosine
kinase
Ph chromosome seen in ALL produces p210 and
chronic neutrophilic leukemia produces p230
Karyotype 46,XX,t(9;22)(q34;q11.2) -- Ph chromosome
FISH showing the BCR (green), ABL (orange), and BCR-ABL fusion
signals (arrow): A=positive (contains a residual ABL signal), B=normal
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
WHO Classification of MPS
(1997)
CML becomes
CML, Ph + t(9;22) BCR/ABL