• A 4 years old boy is taken by his parents to the pediatrician because of

vomiting, headaches, and tenderness in the bones of his arms and legs:
On palpation, the physician notes many lymph nodes are enlarged, as is
the liver. The pediatrician should order a complete blood count in order
to determine whether or not the child may have
• a) Chronic leukemia
• b) Infectious mononucleosis
• c) von Willebrand disease
• d) Acute leukemia
• e) Pernicious anemia
ACUTE LEUKEMIA
ACUTE LEUKEMIA CHRONIC LEUKEMIA
BLASTS + -
TdT + -
AGE
ACUTE LEUKEMIA
ALL AML
AGE CHILDREN -ADULTS
MPO - +
TdT + -
 ACUTE LEUKEMIA

BONE MARROW
BLASTS

MYELOBLAST
LYMPHOBLAST TdT
MPO(auer rods)

PRECURSOR B PRECURSOR T CELL

CELL TYPE(CD10, TYPE CD1.CD2.
CD19, CD20, CD23 CD5
ACUTE LEUKEMIA: LYMPHOCYTE
ANTIGEN
PRIMARILY T CELL ASSOCIATED PRIMARILY B CELL ASSOCIATED
CD1 CD10
CD2 CD19
CD3 CD20
CD4 CD21
CD5 CD22
CD6 CD23
CD7
CD8
 MYELOID LYMPHOID
DISORDERS DISORDERS
BONE MARROW MYELOBLASTS-- ACUTE MYEOID LYMPHOBLAST ACUTE
LEUKEMIA LYMPHOBLASTIC
LEUKEMIA
BLOOD RED CELLS POLYCYTHEMIA T CELL B CELL CHRONIC
VERA LYMPHOCYTIC
PLATELETS ESSENTIAL LEUKEIA
THROMBOCYTSIS
GRANULOCYTES CHRONIC MYELOID
LEUKEMIA
LYMPH NODE T CELL B CELL LYMPHOMA

BONE MARROW PLASMA CELL PLASMA CELL

(RETURN)
ACUTE LEUKEMIA
BASIC NEOPLASTIC PROLIFERATION OF BLASTS, DEFINED AS THE ACCUMULATION OF
HIGH THAN 20% BLASTS IN THE BONE MARROW.
PRINCIPLES
INCREASED BLASTS”CROWS-OUT NORMAL HEMATOPOIESIS, RESULTING IN AN
“ACUTE” PRESENTATION WITH ANEMIA(FATIGUE),
THROMBOCYTOPENIA(BLEEDING, OR NEUTROPENIA(INFECTION)

BLASTS USUALLY ENTER THE BLOOD STREAM, RESULTING IN A HIGH WBC

CPNT.; BLAST ARE LARGE, INMATURE CELLS, OFTEN WITH PUNCHED OUT
NUCLEOLI

ACUTE LEUKEMIA IS SUBDIVIDED INTO ACUTE LYMPHOBLASTIC LEUKEMIA

(ALL) OR ACUTE MYELOGENOUS LEUKIMIA (AML) BASED ON THE PHENOTYPE
OF THE BLASTS
 ACUTE LYMPHOBLASTIC LEUKEMIA ACUTE LYELOID LEUKEMIA
MPO -- +-
TdT +
ACUTE
LYMPHOBLASTIC
A. NEOPLASTIC ACCUMULATION OF
LEUKEMIA LYMPHOBLASTS(HIGH THAN 20%) IN THE BONE MARROW

1. LYMPHOBLASTS ARE CHARACTERIZED BY POSITIVE

NUCLEAR STAINING FOR TdT, A DNA POLYMERASE

2. TdT IS ABSENT IN MYELOID BLASTS AND MATURE

LYMPHOCYTES.
ACUTE
LYMPHOBLASTIC B. MOST COMMONLY ARISES IN CHILDREN,
LEUKEMIA
ASSOCIATED WITH DOWN
SYNDROME( USUALLY ARISES AFTER THE AGE
OF 5 YEARS)
C. SUBCLASSIFIED INTO B-ALL AND T-ALL
BASED ON SURFACE MARKERS
ACUTE D. BALL IS THE MOST COMMON BY LYMPHOBLASTS(TdT+) that express cd10, cd19,
LYMPHOBLASTIC and cd20
LEUKEMIA

2. EXCELLENT RESPONDE TO CHEMOTHERAPY; REQUIRES PROPHYLAXIS TO SCROTU

AND CSF
3. PROGNOSIS IS BASED ON CYTOGENETIC ABNORMALITIES.

I. y(12.21) HAS A GOOG PROGNOSIS,MORE COMMONLY SEEN INCHILDREN

II. T(9:22) HAS A POOR PROGNOSIS, MORE COMMONLY SEEN IN

ADULTS(PHILADELPHIA+ALL)
ACUTE T-ALL IS CHARACTERIZED BY LYMPHOBLASTS/TdT+) THT
LYMPHOBLASTIC
LEUKEMIA
EXPRESS MARKERS RANGING FROM CD2 TO CD8. THA BLASTS
DO NOT EXPRESS CD10.

I. USUALLY PRESENTS IN TEENAGERS AS A

MEDIASTINAL(THYMIC MASS(CALLED ACUTE LYMPHOBLASTIC
LYMPHOMA BECAUE THE MALIGNANT CELLS FORM A MASS.
ACUTE A. NEOPLASTIC ACCUMULATION OF IMMATURE MYELOID
LYMPHOBLASTIC
LEUKEMIA
CELLS HIGH THAN 205 IN THE BONE MARROW.

B, MYELOBLASTS ARE USUALLY CHARACTERIZED BY POSITIVE

CYTOPLASMIC STAINING FOR MYELOPEROXIDASE (MPO);
CRISTAL AGGREGATES OF MPO MAY BE SEE AS AUER RODS

C. MOST COMMONLY ARISES IN OLDER ADULTS(AVERAGE AGE

IS 50-60 YEARS)
ACUTE D. SUBCLASSIFICATION BASED ON CYTOGENETIC ABNORMALITIES,LINEAGE OF IMMTUTE MYELOID
CELLS, AND SURFACE MARKERS. HIGH.YIEL SUBTYPES INCLUDE
LYMPHOBLASTIC
LEUKEMIA
1. ACUTE PROMYELOCYTIC LEUKEMIA

CHARCTERIZED BY T(15;17), WHIDH INVOLVESTRANSLOCATION OF THE RETINOIC ACID

RECEPTOR(RAR) ON CHROMOSOME 17 TO 15;RAR DISRUPTION BLOCKS MATURATION AND
PROMYELOCYTES8blasts) ACCUMULATE)

ABNORMAL PROYELOCYTES CONTAIN NUMEROUS PRIMARY GRANULES THAT INCREASE THE RISK
FOR DIC.

TREATMENT IS WITH ALL-TRANS-RETINOIC(ATRA, AVITAMIN DERIVATIVE), WHICH BINDS THE

ALTERED RECEPTOR AND CAUSES THE BLASTS TO MATURE(AND EVENTUALLY DIE)
ACUTE
LYMPHOBLASTIC 2. ACUTE MONOCYTIC LEUKEMIA
LEUKEMIA

PROFIFERATION OF MONOBLASTS;
USUALLY LACK MPO
BLASTS CHARACTERISTICALLY
INFILTRATE GUMS
ACUTE
LYMPHOBLASTIC 3. ACUTE MEGAKARYOBLASTIC LEUKEMIA
LEUKEMIA

PROLIFERATION OF MEGAKARYOBLASTS; LACK

MPO

ASSOCIATED WITH DOWN SYNDROME(USUALLY

ARISES BEFORE THE AGE OF 5)
ACUTE E. AML MAY ALSO ARISE FROM PRE-EXISTING DISPLASIA
LYMPHOBLASTIC (MYELOYSPLACTIC SYNDROMES), ESPECIALLY WITH PRIOR
LEUKEMIA EXPOSURE TO ALKYLATING AGENTS OR RADIOTHERAPY

1. MYELODYSPLASTIC SYNDROMES USUALLY PRESENT WITH

CYTOPENIAS, HYPERCELLULAR BONE MARROE, ABNORMAL
MATURATION OF CELLS, AND INCREASED BLASTS(LOW THAN 20%)

2. MOSTPATIENTS DIE FROM INFECTION OR BLEEDING, THOUGH-

SOME PROGRESS TO ACUTE LEUKEMIA.
ACUTE
LYMPHOBLASTIC
LEUKEMIA
ACUTE LEUKEMIA

ACUTE M0 UNDIFFERENTIAL

MYELOID M1 EARLY MYELOBLASTIC

LEUKEMIA M2 MYELOCYTIC
M3 PROMYELOCYTIC
M4 MYELOMONOCYTIC
M5 MONOCYTIC/ MONOBLASTIC
M6 ERYTHROID
M7 MEGACARIOCYTIC
ACUTE LEUKEMIA

ACUTE A. NEOPLASTIC ACCUMULATION IF IMMATURE MYELOID

CELL HIGH THAN 20% IN THE BONE MARROE
MYELOID
LEUKEMIA B. MYELOBLASTS ARE USUALY CHARACTERIZED BY POSITIVE
CYTOPLASMIC STAINING FOR MYELOPEROXIDASE(MPO)

CRYSTAL AGGREGATES OF MPO MAY SEEN AS AUER RODS

C, MOST COMMONLY ARISES IN OLDER ADULTS ( AVERGE

AGE IS 50-89 YEARS)
ACUTE LEUKEMIA

ACUTE D. SUBCLASSIFICATION BASED ON CYTOGENETIC

MYELOID ABNORMALITIES, LINAGE OF IMMATURE MYELOID CELLS,
AND SURFACE MARKERS. HIGH YIELD SUBTYPES INCLUDE
LEUKEMIA
ACUTE LEUKEMIA

ACUTE E. AML MAY ALSO PRIOR FROM PRE-EXISTIN

DYSPLASIA( MYELODYSPLACTIC SYNDROMES), ESPECIALLY WITH
MYELOID PRIOR EXPOSURE TO ALKYLATING AGENTS OR RADIOTHERAPY.
LEUKEMIA
MYELODYSPLACTIC SYNDROMES USUALLY PRESENT WITH
CYTOPENIAS, HYPERCELLULAR BONE MARROW, ABNORMAL
MATURATION OF CELLS, AND INCREASED BLAST(LOW THAN 20%)

MOST PATIENTS DIE FROM INFECTION OR BLEEDING, THOUGH

SOME PROGRESS TO ACUTE LEUKEMIA
CASES FILES
• A mother brings her 6-years-old son to his pediatrician because he
has having recurrent nosebleeds. physical examination reveals diffuse
petechiae. laboratory studies show:
• complete blood count
-Hemoglobin 9.0g/l
-Platelet count 20.000/mm3
-Leukocyte count 14.500/mm3
• Bone marrow aspiration reveals the following:
CASES FILES
• Bone marrow aspiration reveals the following:
CASES FILES
• The large cells at hte center of the slide demonstrate positive
immunostaining for terminal deoynucleotidyltransferase(TdT. They
express Surface CD19 and CD10 as well. What is the most likely
diagnosis?
• A. Precurcor- B cell leukemia
• B. Precurssor T- cell leukemia
• C. Mature B-cell leukemia
• D. Mature T- cell leukemia
• E. Hodgkins lymphoma
WHICH OF THE FOLLOWING CHROMOSOMAL
ABNORMANALITIES IS MOST LIKELY PRESENT IN THE
AFFECTED CELLS
• A. t(8;14)
• B. t(9;22)
• C. t(11;14)
• D. t(15;17)
• E. 13q
CHRONIC LEUKEMIA
BASIC A. NEOPLASTIC RPOLIFERATION OF MATURE
PRINCIPLES CIRCULATING LYMPHOCYTES CHARACTERIZED BY A HIGH
WBC COUNT

B. USUALLY INSIDIOUS IN ONSET AND SENN IN OLDER

ADULTS
CHRONIC LEUKEMIA
CHRONIC A. NEOPLASTIC PROLIFERATION OF NAIVE B CELLS THAT CO-
LYMPHOCYTIC EXPRESSCD5 AND CD20; MOST COMMON LEUKEMIA OVERALL
LEUKEMIA(CLL)
B. INCREASED LYMPHOCYTES AND SMUDGE
CHRONIC LEUKEMIA: CHRONIC
LYELOGENOUS LEUKEMIA
MALIGNANT DISORDER OF MYELOID
PROGENITOR CELLS
DYSREGULATED PRODUCTION

CLASSIFIED AS A MYELOPROLOFERATIVE
DISORDER
CHRONIC LEUKEMIA

MALIGNANT PROLIFERATION OF WHITE

BLOOD CELLS
CELLS APPEAR IN BLOOD(CONTRAST
WITH LUMPHOMA)
INCREASED WBC
CHRONIC LEUKEMIA
PERIPHERAL BLOOD(CHRONIC PHASE)
LEUKOCYTOSIS
NEUTROPHILS
BASOPHILS
EOSIPHILS
MILD ANEMIA;NORMAL OR INCREASED PLATELETS
CHRONIC LEUKEMIA
CAN BE ASYMPTOMATIC(HIGH WBC ON BLOOD TESTING)
CHRONIC FATIGUE, MALAISE, WEIGHT LOSS, SPLENOMEGALY
PHASE(USUALLY YEARS)
FEW BLAST(USUALLY LOW THAN 2%)

TREATMENT FAILURE(RISING WBC)

ACCELERATED PHASE

ACUTE LEUKEMIA (HIGH THAN 20% IN PERIPHERY OR

BLAST CRISIS MARROW)
USUALLY MYELOBLASTS(AML)

LESS COMMONLY LYMPHOBLASTS(ALL)

CHRONIC LEUKEMIA
LEFT SHIFT:
LEUKEMOID NORMAL RESPONDE TO INFECTION
REACTION

MORE BANDS AND NEUTROPHILS

MUST BE DISTINGUISHED FROM CML

CHRONIC LEUKEMIA
LEUKOCYTE ENZIME FOUND IN NORMAL NEUTROPHILS
ALKALINE
PHOSPHATASE
ABSENT IN NEUTROPHILS OF CML

ENZIME LEVEL ASSESSED WITH LAP SCORE LOW= CML

HIGH= LEUKEMOID REACTION
LARGELY REPLACED BY TESTING FOR PH CHROMOSOME
CHRONIC LEUKEMIA
PHILADELPHIA
CHROMOSOME GENETIC HALLMARK OF CML
9:22 TRANSLOCATION
BCR-ABL FUSION GENE
SYNTHESIS TYROSINE KINASE PROTEIN
LONG CELL LIFE--ACCUMULATION
CHRONIC LEUKEMIA
TYROSINE IMATINID,DASATINID, NILOTINID
KINASE
INHIBITORS
USED FOR TREATMENT IN CML(CHRONIC PHASE)

LONG TERM CONTROL OF DISEASE

BONE MARROW TRANSPLANT OFTEN USED AFTER

FAILURE
CHRONIC LEUKEMIA: CHRONIC LYMPHOCYTIC LEUKEMIA

DISORDER OF NAIVE LYMPHOCYTES: NO

BLASTS, NEWLY PRODUCED BONE MARROW

CHARACTERISTIC INMUNOPHENOTYPE:
CD5+B CELLS

CO.EXPRESS CD20 AND CD5

CHRONIC LEUKEMIA: : CHRONIC
LYMPHOCYTIC LEUKEMIA
SMALL SAME MALIGNANT CELLAS CLL
LYMPHOCYTIC
LYMPHOMA
DIFFERENTIATED BY DEGREE OF LYMPHOCYTOSIS

CLL: INCREASED WBC HIGH THAN 5000

SLL: NORMAL OR MILD LYMPHOCYTOSIS LOW THAN 5000

CHRONIC LEUKEMIA: CHRONIC
LYMPHOCYTIC LEUKEMIA
MEDIAN AGE 60

PATIENTS OFTEN ASYMPTOMATIC: INCREASED

LYMPHOCYTES:5-10% OF PATIENTS HAVE B SYMPTOMS
SIGNS: LYMPHADENOPATHY, SPLENOMEGALY,
HEPATOMEGALY
MANY PATIENTS OBSERVED WITHOUT TREATMENT
CHRONIC LEUKEMIA: CHRONIC
LYMPHOCYTIC LEUKEMIA
SMUDGE PERIPHERAL LYMPHOCYTES ARE
CELLS
FRAGILE

DISRUPTED DURING
PREPARATION OF BLOOD SMEAR
CHRONIC LEUKEMIA: CHRONIC
LYMPHOCYTIC LEUKEMIA
HYPOGAMMAGLOBULINEMIA: USUALLY LOW OF IgG, IgA,IgM;

INCREASED SUSCEPTIBILITY TO
BACTERIAL INFECTIONS

AUTOANTIBODIES: NOT PRODUCED BY MALIGNANT CELLS

PRODUCED BY NON-NEOPLASTIC
CELLS(SELLF-REACTIVE)
AUTOIMMUNE HEMOLYTIC ANEMIA
CHRONIC LEUKEMIA: CHRONIC
LYMPHOCYTIC LEUKEMIA
MAY TRANSFORM INTO
DIFFUSE LARGE B CELL
LYMPHOMA– RICHTER
TRANSFORMATION
PATIENT WITH KNOWN CLL
CLASSIC
PRESENTATION: RAPID GROWTH OF SINGLE LYMPH NODE

BIOPSY: DIFFUSE LARGE B CELL

LYMPHOMA