Case Study …

A 53-years old man presented with three weeks history of moderate shortness in breath , weight and appetite loss , and he sometimes suffering from fever and night sweats, also its found that he has abdominal distention, on physical examination Abdominal palpation shown an enlargement in spleen. He asked for examination which include CBC , blood film, bone marrow examination and cytogenetics.

CBC with differential results: Hb 10.1g/dl RBC count 3.7x 10^6cells/μL WBC count 130,000 cells/μL Plt count 435,000 cells/μL MCH 28.4 pg MCV 84 fl Neutrophil % 54% Lymphocyte % 10% Basophil % 4% Promeylocyte % Metamyelocyte % 5% Myelocyte Blast cells % 2% band cells % 13% monocyte Normocytic Normochromic anemia Increased WBCs count with immature myeloid form. Plt count increased When make biochemistry examination LDH was 1500 IU/L and Uric acid 10.4 mmol/L

Blood Film :

Bone Marrow examination : Bone marrow aspirate showed an increased cellularity with myeloid hyperplasia and a marked basophilia. Megakaryocytes were also increased. Trephine demonstrated marked hypercellularity with loss of fat spaces and no evidence of bone marrow fibrosis.

Cytogenetics : cytogenetic analysis demonstrated the typical translocation between chromosome 9 and 22. Ph. chromosome +

Chronic Myeloid Leukemia After presenting the results of examination, we expected that he has : Chronic Myeloid Leukemia

Chronic Myeloid Leukemia (CML) : CML is defined as a stem cell disorder suggested as Philadelphia chromosome found in all stem cells. So there is replacement of normal B.M cells by cells with an abnormal chromosome-Philadelphia or (ph) chromosome t (9; 22)(q34; q11).

Philadelphia chromosome : Is the chromosome which result from the t(9;22)(q34;q11), part of the Abelson proto-oncogene ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome 9. The abnormal chromosome 22 is the Ph.

Normal ABL gene encode protein P145 which has tyrosine kinase activity and play role in regulation of several different growth factor receptors, including those for epidermal growth factor, Plt derived growth factor, and colony stimulating factor receptor. Normal BCR gene encode protein P160 which known to has serine/threonine kinase activity and it play important role in cellular transduction. BCR-ABL fusion gene produce a protein (P210) this protein has much more powerful tyrosine kinase activity than P145 And it has a great serine/threonine activity that enhance proliferation and differentiation.

Clinical Presentation : Increasing splenomegaly, which is associated with discomfort, pain or indigestion. Refractory anemia that include pallor, weakness and tachycardia. Bruising, epistaxis due to abnormal platelet functions. Gout or renal impairment due to hyperuricemia. Visual disturbances. Increase requirement to chemotherapy to maintain remission. Massive increasing of circulating granulocytes.

Phases of CML: Chronic phase Accelerated phase Blast phase

Chronic Phase : The three defining features of typical chronic phase are: Raised granulocytes. The presence of Philadelphia chromosome. Splenomegaly. Fewer than (10%) of the blood cells in your bone marrow are immature white blood cells known as blasts.

Accelerated Phase: >15% blasts in B.M or peripheral blood. >30% blasts + promyelocyte in peripheral blood. >20% basophil in peripheral blood. <100,000/m3 platelet. Additional chromosome abnormality (+8) trisomy Increase bone marrow fibrosis

Blast Phase : In most cases, establishment of the accelerated phase of CML is followed by a sustained refractory to treatment, the blast cell count rises and physical symptoms are worsening. The diagnostic criteria for blast crisis are that the circulating blast cell counts should exceed 30% of the total leukocyte count. Progression of chronic phase to Blastic phase has been likened to the evolution of chronic leukemia into acute leukemia. The accumulation of blast cells which results is accompanied by anemia, neutropenia and thrombocytopenia.

Prepared by : Lamees Al Farra Azza Al Danaf