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#chronicmyeloidneoplasm|#CML|#MYELOPROLIFERATIVENEOPLASM|#WHOCLASSIFICATION
INTRODUCTION
Chronic
myeloid leukemia is a clonal hematopoietic neoplasm characterised by BCR-ABL
Fusion resulting in the formation of PHILADELPHIA CHROMOSOME.
DEFINITION
Chronic
myeloid leukaemia is a myeloproliferative neoplasm.
Characterized
by granulocytic proliferation.
SYNONYMS
Chronic
myelogenous leukaemia, BCR-ABL POSITIVE
Chronic
myelogenous leukaemia, PHILADELPHIA CHROMOSOME POSITIVE (Ph+)
Chronic
myelogenous leukaemia t(9;22)(q34;q11)
Chronic
granulocytic leukaemia ,BCR-ABL positive
Chronic
granulocytic leukaemia, Philadelphia positive(ph+)
Chronic
granulocytic leukaemia t(9;22)(q34;q11)
EPIDEMIOLOGY
INCIDENCE:
1-2 cases per 100000 population.
Males
are affected than females.
ETIOLOGY
UNKNOWN
Radiation
exposure may be implicated due to increase incidence of cases in Atomic bomb
survivors.
CLINICAL FEATURES
Approximately
50% of newly diagnosed cases are asymptomatic.
Common
clinical findings include-
Lethargy
Fatigue
Weight
loss
Night
seats
Anaemia
Palpable
splenomegaly
MOLECULAR GENETICS
Phenotype
of the disease depends on the site of breakpoint in the chromosome 22.
Major BCR :BCR in the exons 12-16 (b1-b5)-> abnormal fusion
protein p210.
Minor BCR : BCR in the exons 1-2->short fusion protein p190 ,
associated with Ph+ ALL and monocytosis.
Micro BCR: BCR in the exons 17-20(c1-c4)->large fusion protein
p230 associated with marked thrombocytosis and /or neutrophilic maturation.
GROSS PATHOLOGY
SPLEEN-
solid with uniform bright red colour and light coloured regions indicate areas
of infarction.
LIGHT MICROSCOPY
Leukemic
cells are usually found in splenic cords and sinuses.
White
pulp is obliterated by neoplastic cells.
DIAGNOSIS
PERIPHERAL
BLOOD EXAMINATION
BONE
MARROW EXAMINATION
CYTOGENETICS
MOLECULAR
ANALYSIS – to identify the Ph chromosome or BCR-ABL 1 fusion.
PERIPHERAL SMEAR EXAMINATION
Marked leucocytosis ranging from 20-500X109/L.
Myelocytes are more in number than Meta myelocytes (Myelocyte bulge).
No or very minimal dysplasia.
Low neutrophil/leukocyte alkaline phosphate.
Absolute basophilia in almost all cases.
Absolute
eosinophilia in nearly all cases.
BONE MARROW
Hypercellular
marrow
M:E
ratio increased (up to 20:1)
15-20
cell thickness of immature para trabecular cuff.
Low
blast count
Megakaryopoiesis
increased , small hypolobated nucleus
(dwarf megakaryocyte).
20-40% cases show pseudogaucher cells (characteristic crumpled tissue paper like cytoplasm which usually shows hemophagocytosis.
Thrombocytosis is commonly seen.
STAGES OF CML
ADJUNCTIVE TESTS
LAP
score low , it can be used as screening test , however increased NAP score is
seen in accelerated phase of CML.
Raised
Vitamin B12 levels.
Raised
Uric acid levels.
ANCILLARY TESTS
Demonstration
of BCR-ABL 1 fusion gene
Conventional
cytogenetic analysis
FISH
with probes to BCR and ABL1
POLYMERASE
CHAIN REACTION
DIFFERENTIAL DIAGNOSIS
Leukemoid
reaction
Atypical
CML (Ph negative , BCR-ABL1 negative)
Chronic
Neutrophilic leukemia
CMML
Cellular
phase of Myelofibrosis
PROGNOSIS AND PREDICTIVE FACTORS
SOKAL
SCORE-Age , Spleen size , Platelet count , % blasts.
EUTOS
SCORE-
REMISSION RATE IN CHRONIC MYELOID
LEUKEMIA
COMPLETE
HEMATOLOGICAL RESPONSE:
PARTIAL
CYTOGENETIC REMISSION
COMPLETE
CUYTOGENETIC REMISSION
MAJOR
MOLECULAR RESPONSE
COMPLETE
MOLECULAR RESPONSE
Monday, February 8, 2021
Tuesday, February 2, 2021
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