This document discusses chronic myeloid leukemia (CML), a myeloproliferative disorder originating from stem cells characterized by the Philadelphia chromosome. The key points are: CML is caused by the BCR-ABL fusion gene resulting from a translocation between chromosomes 9 and 22, which encodes for uncontrolled tyrosine kinase activity. This leads to increased proliferation of myeloid cells. CML progresses through three phases: chronic, accelerated, and blastic (acute) phases as the disease becomes more aggressive and chemotherapy-resistant over time. Diagnosis involves blood tests showing leukocytosis with immature cells, elevated LDH and basophils, and bone marrow biopsy demonstrating hypercellularity and myeloid hyper

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Dr mustafa ali

2. Define
Etiology
Classification
Diagnosis

3. A myeloproliferative disorder originates
from stem cell , characterized by
Leucocytosis with granulocytic
immaturity, basophilia, splenomegaly
and distinct chromosomal abnormality
–Philadelphia (Ph).

4.  Ionizing radiation
Survivors of Hiroshima and Nagasaki
Patients of ankylosing spondylitis
 HLA, CW3, CW4
 ABL proto oncogenes from chromosome 9
is translocated to chromosome 22 where
BCR is present and result in formation of
BCR-ABL fusion chimeric gene

6. BCR-ABL fusion gene
Impedes apoptosis Encodes for tyrosine kinase activity
↑ Tyrosinase kinase of stem cell
Uncontrolled proliferation of myeloid cells
Chronic myeloid leukemia

9. 3 Phases
(1) Chronic Phase
(2) Accelerated Phase
(3) Blastic Phase

10. Stable phase
Lasts for 2-6 years
Blast cells 2-5% in blood / marrow
Gradually transformed into accelerated
phase
Abruptly may transformed in to blastic
phase

11. More aggressive phase
Lasts for few months
Usually transformed in to blastic phase
Blast cells 10-20% blood / marrow
Spleen fail to regress with treatment or
size starts increasing

12. Blast cells >20% blood / marrow
Lymphadenopathy may present
Lasts for few weeks to month
Marrow fibrosis may develop
Granulocytic sarcoma may develop
Basophile >20%
Thrombocytopenia leads to bleeding

13. Juvenile myelomonocytic leukemia
 Chronic myelomonocytic leukemia

Eosinophilic leukemia

Granulocytic sarcoma

14. Peripheral blood examination
Bone marrow examination
Biochemical parameter

15.  Hb decreased
 Leucocytosis (1-5 lack)
 Immature myeloid cells
Blast cells 1-5%
Promyelocytes 4-10%
Myelocytes 30-40%
Metamyelocytes 20-30%
Neutrophils 30-50%
 Basophilia
 Eosinophilia
 Platlets count :- normal or increased

17. MYELOBLAST
BAND CELLS
PROMYELOCYTES
MYELOCYTES

19.  Marked hyper cellular
 Marked myeloid hyperplasia
 Presence of basophiles and eosinophil and their
precursor
 Erythroid precursor decrease
 Megakaryocyte normal or increased
 Gaucher like cells :- large histiocytes (Pseudo Gaucher
cells) , sometimes with blue granules (Acquired Sea
Blue Histiocytes)
 Variable degree of marrow fibrosis

21. NAP score :- decreased 0-20 (Normal
40-100)
Serum uric acid :- increased due to
high turnover of whites cells
Serum LDH :- increased
Serum Alkaline Phosphatase :-
increased
Transcobalamine-1 level :- increased

22. 3 sub types
(1.) classical chronic granulocytic
leukemia (CGL) Ph+ BCR+ / PH- BCR+
(2.) chronic myelomonocytic leukemia
(CMML)
(3.) atypical CML (aCML) resemble
classical CGL but are PH- BCR-

23. CGL aCML CMML
Basophils ≥ 2% < 2% < 2%
Monocytes < 3% ≥3-10% ≥ 3-10%
Granulocytes
dysplasia
- ++ +
Immature
granulocytes
>20% 10-20% ≤ 10-%
Blasts < 2% > 2% < 2%

24. FEATURE LEUKEMOID
REACTION
CML
Nature of disease Reactive Stem cell MPD
Causes of leukemoid
reaction
+ve -ve
Splenomegaly -ve +ve
TLC 10,000-50,000/l 1-5 lacks/l
Toxic granules in
neutrophils
+ve -ve
Basophilia -ve +ve
Eosinophilia -ve +ve
NAP score (150-350) (0-40)
Ph chromosomes -ve +ve

25. FEATURE CML MF
Stem cell Stem cell disease Not a stem cell
disorder
Ph chrosome +ve -ve
TLC 1-5 lacks/l <50 ,000/l
Blood picture Blasts,promyelocytes
,myelos ,Metas
present
Leuoerythroblastic
blood picture
Basophilia &
Eosinophilia
+ve -ve
Tear drop cells -ve +++
Myeloid hyperplasia
BM
+++ ±
NAP score < 40 > 100
Fate (transform to) blastic phase extensive fibrosis
with marrow failure