chronic myeloproliferative neoplasm

1. CHRONIC MYELOID
LEUKEMIA
Dr. Anshita Dubey

2. CML is a Chronic myeloproliferative neoplasm characterised by
predominant proliferation of granulocytic cells.

4. Pathogenesis
• Neoplastic transformation of stem cell overproduction of
normal appearing granulocytes
• Hallmark : Ph chromosome reciprocal translocation of 9 and 22

5. ABNORMAL CONSECUTIVELY ACTIVE TYROSINE KINASE
MODULATE TRANSCRIPTION FACTORS RELATED TO CELL
PROLIFERATION, SURVIVAL, DIFFERENTIATION
DNA OXIDATIVE DAMAGE ; BLOCKAGE OF REPAIR PATHWAYS
PRONE TO DELETERIOUS MUTATIONS
Duplication of Ph, +18, +19 and -Y

6. CLINICAL FEATURES
• 40- 50 years ; males
• Fatigue,fever
• Sweating
• Weight loss
• Hepatosplenomegaly – extramedullary hematopoiesis

7. Diagnosis
Phases
• Chronic
• Accelarated
• Blast crises

8. CHRONIC PHASE
PERIPHERAL BLOOD SMEAR
• WBC – 30 * 10 9/ l to 500*109/L
• Neutro and myelocytes
• High Basophils
• Blasts <2% IN PBS; <5% in BM
• Eosinophilia
• Monocytosis
• Macrocytosis : (overproduction of myeloid – folate deficiency)
• Nap score : 0-20 (n – 40-100)

9. • Nap stain : The neutrophil alkaline
phosphatase (synonym: leukocyte
alkaline phosphatase, LAP) is
present in the cytoplasm and
secondary granules of
neutrophils.
Principle :

10. Bone marrow
• Hypercellular with high M:E ratio.
• Megakaryocytes : dwarf platelets/micromegakaryocytes with
dysmegakaryopoiesis seen in paratrabecular zone.
• Erythroid series : decreased & morphologically normal
higher number s/o good prognosis
• Pseudogaucher cells , sea blue histiocytes : due to increased turnover from
granulocytic membranes.

11. Accelarated Phase Criteria

12. Criteria of blast crises phase
• Blasts> 20% of PBS or bone marrow
• Extramedullary blast proliferation
• Large foci of blasts in the bone marrow biopsy

13. FISH

14. PROGNOSIS
Most important prognostic factor : response to TKI
Response : optimal / failure
• HEMATOLOGICAL
• MOLECULAR
• CYTOGENETIC

15. CHR : WBC <1*109/l; basophils < 5 %; no circulating granulocyte
precursors; platelet count <450*109/l; no splenomegaly
CCyR : no Ph1 positive metaphases detected in 2 successive bone
marrow samples after counting 20 metaphases
Term CMR is avoided; molecularly undetectable leukemia with
specification of number of control gene transcripts

18. IMMUNOPHENOTYPING
Expression of CD7 on CD34+ cells – ADVERSE PROGNOSIS
LACKING CD7, CD56,or CD11 b – BETTER RESPONSE TO TKI
CD33, CD13, CD14, CD11b, CD11c, KIT(CD117), CD15, CD41, CD61, and glycophorin
A and C.
Most lymphoblastic BP blasts - B-cell origin : terminal deoxynucleotidyl transferase
(TdT) & B-cell-related antigens (e.g. CD19, CD10, CD79a,PAX5, and CD20)
Minority lymphoblastic BP blasts - T-cell origin : T-cell-related antigens
(e.g. CD3, CD2, CD5, CD4, CDS, and CD7)

19. Flow cytometry -Preferred technique for phenotypic analysis
Immunohistochemical stains :
• If a marrow aspirate cannot be obtained
• Insufficient numbers of blasts in the blood
LYSOZYME

20. Myeloperoxidase
Principle : MPO splits H2O2 in the presence of chromogenic electron
donor(DAB) and forms an insoluble reaction product which is stable
insoluble and non diffusible.

21. Differential diagnosis
• Leukemoid reaction
• Cellular phase of idiopathic myelofibrosis