Chronic myeloproliferative disorders
Definition
MPD describes a group of conditions characterized by clonal proliferation of one or more hematopoietic components in the BM and in many cases the liver and the spleen.
Types of MPD
• Chronic myeloid leukemia (CML or CGL).
• Polycythemia Vera
• Essential Thrombocythaemia
• Idiopathic myelofibrosis
Relationship of various MPD to each other Relationship of various MPD to each other
Bone marrow stem cells
Cellular proliferation
Granulocyte Precursors
Red cell
precursors Megakaryocytes Reactive fibrosis
Clinical
entity CML Polycythemia
Vera
Essential
thrombocythemia
Myelofibrosis
AML
Acquired Abnormality
CML CML
Clonal
Clonal stem cell disorder. stem cell disorder.
Exposure to Ionizing radiation or chemical Exposure to Ionizing radiation or chemical
leukemogens
leukemogens ( ( ch ch . Drugs) . Drugs)
Clinical features:
Clinical features:
Occurs in either sex (
Occurs in either sex ( male:female male:female , 1.4:1). , 1.4:1).
Most frequently between the ages of 40
Most frequently between the ages of 40 - - 60. 60.
Wight lost, anorexia, night sweats.
Wight lost, anorexia, night sweats.
Splenomegaly
Splenomegaly is always present and is frequently is always present and is frequently massive.
massive.
Feature of
Feature of anemia anemia
Philadelphia chromosome Philadelphia chromosome
Over 95% of CML patients there is a Over 95% of CML patients there is a
replacement of normal BM by cells with an replacement of normal BM by cells with an
abnormal chromosome (Philadelphia abnormal chromosome (Philadelphia
chromosome) chromosome)
–– Ph chromosome due to the Ph chromosome due to the traslocationtraslocation of part of a of part of a long arm (q) of chromosome 22 to a part of
long arm (q) of chromosome 22 to a part of chromosome 9 including the ABL
chromosome 9 including the ABL OncogeneOncogene..
–– t(9;22) :ct(9;22) :c--ABL ABL OncogeneOncogene from from chch 9 is 9 is translocatedtranslocated to to chch 22 at the breakpoint cluster region (BCR) to give 22 at the breakpoint cluster region (BCR) to give
the BCR
the BCR--ABL fusion gene.ABL fusion gene.
Philadelphia chromosome
Philadelphia chromosome
Philadelphia chromosome
Philadelphia chromosome
BCR BCR - - ABL ABL
BCR BCR - - ABL detection by RT ABL detection by RT - - PCR PCR
Antityrosine
Antityrosine kinase kinase
Laboratory diagnosis Laboratory diagnosis
CBC (left shifting) CBC (left shifting) Leukocytosis
Leukocytosis >50 >50 ×× 109/l109/l
Morphology of PB shows a complete spectrum of Morphology of PB shows a complete spectrum of myeloid cells seen in the PB.
myeloid cells seen in the PB.
Decreased NAP score.
Decreased NAP score.
BM is
BM is hypercellularhypercellular with with granulopoieticgranulopoietic predominance.predominance.
Increased circulating
Increased circulating basophilsbasophils.. SerumVit
SerumVit B12 and B12 and VitVit B12B12--binding capacity are binding capacity are increased. Serum uric acid is usually raised.
increased. Serum uric acid is usually raised.
Cytogenetic
Cytogenetic analysis of PB and BM showed Ph analysis of PB and BM showed Ph chromosome (BCR/ABL fusion gene.
chromosome (BCR/ABL fusion gene.
Normal Peripheral Blood
CML Peripheral blood
PB BM
NAP +ve NAP -ve
NAP Score
NAP Score
Chronic Myelogenous Leukemia Reactive Granulocytosis Pathophysiology Clonal, autonomous proliferation of
hematopoietic cells
Cytokine induced increase in bone marrow production, release and demargination of granulocytes, secondary to infection or inflammation Clinical Features Patient often asymptomatic
Splenomegaly
•Signs of infection or inflammation
Laboratory studies
CBC Granulocytosis with left shift Thrombocytosis
Basophilia
Granulocytosis with left shift Thrombocytosis (rarely > 1 x 106/mm3)
LAP Score Decreased q Normal or increased Cytogenetic studies Philadelphia Chromosome present Normal
Molecular studies Chimeric bcr-abl gene present by FISH and PCR analysis
Normal
Treatment Hydroxyurea, Interferon-a, Stem cell transplant
Treat underlying cause Comparison of CML and Reactive Granulocytosis
