A 60 year old man presented with fatigue, weight loss and heaviness in left hypochondrium for 6 months. The hemogram showed Hb 10gm/dL, TLC 5 lakhs/mm3, platelet count 4 lakhs/mm3, DLC; neutrophil 55%, lymphocytes 4%, monocytes 2%, basophils 6%, metamyelocytes 10%, myelocytes 18%, promyelocytes 2% and blast 3%. The most likely cytogenetic abnormality in this case is: (AIIMS May 2010)
Chronic Myeloid Leukemia (Ref. Hari- 18th ed., Pg. 914)
Cytogenetic and Molecular Aspects
Ninety percent of patients with CML have Philadelphia chromosomes (Ph). Ph chromosomes occur as a result of reciprocal translocation of material between chromosomes 22 and 9.
Ph' chromosome BCR-ABL fusion gene
1. Ph chromosome is formed as a result of reciprocal translocation between long arm of chromosome 22 and chromosome 9 i.e. t (9; 22) (q 34: q11).
2. ABL protooncogene from chromosome 9 is translocated to chromosome 22 where BCR is present and results in formation of BCR-ABL fusion chimeric gene. (Detected is peripheral blood)
Extra Edge - Clinical Feature
CML affects adults between 25 and 60 years of age, and accounts for 15 to 20% of all cases of leukaemia.
Peak incidence – fourth and fifth decades of life. It is a myeloproliferative disorder with a slight male preponderance.
The course has three phases
1. Chronic phase blast cells <5%– responds to treatment (3 to 5 years)
2. Accelerated phases (occasionally seen)
3. Blast crisis phase – disease transforms into acute leukaemia, either myeloid or lymphatic.
Extra Edge: (Ref. Hari- 18th ed. Pg. 915)
1. Disease acceleration is defined by the development of increasing degrees of anemia unaccounted for by bleeding or therapy; cytogenetic clonal evolution; or blood or marrow blasts between 10 and 20%, blood or marrow basophils 20%, or platelet count <100,000/L.
2. Blast crisis is defined as acute leukemia, with blood or marrow blasts 20%.
3. Hyposegmented neutrophils may appear (Pelger-Huët anomaly).
4. Blast cells can be classified as myeloid, lymphoid, erythroid, or undifferentiated, based on morphologic, cytochemical, and immunologic features.
5. Occurrence of de novo blast crisis or following imatinib therapy is rare.
Extra Edge: Pelger-Huët anomaly = It is characterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.