Hematology Case Study 9
Ms. Karolton, a 35-year old female, was last seen by her physician with complaints of a
20-pound weight loss in the last 6 months, and fatigue. A CBC revealed a WBC count of
56.5x 109/L, hemoglobin of 8 g/dL, and a platlet count of 25x109/L. The leukocyte
differential showed 71% blasts. The bone marrow revealed 96% blasts. The blasts were
negative for myeloperoxidase, sudan black, and combined esterase by cytochemical
stains. Cytogenetics revealed a 9;22 chromosomal translocation
1.
What is the classification of this neoplastic hematologic disorder based on the
peripheral blood and the bone marrow results?
The patient has an acute leukemia as the blast count is> 30% in both the
peripheral blood and bone marrow.
2.
What molecular defect is consistent with the presence of the Philadelphia
chromosome?
The BCR/ABL translocation is the molecular equivalent of the Philadelphia
chromosome. There is a reciprocal translocation between the ABL gene on
chromosome 9 and the BCR gene on chromosome 22. The Philadelphia
chromosome represents the shortened chromosome 22. This fusion gene
produces a new protein having increased tyrosine kinase activity.
3.
Would molecular analysis assist in diagnosis?
Molecular analysis would assist in diagnosis. The patient has the Philadelphia
chromosome associated with CML, but has a peripheral blood and bone marrow
picture of acute leukemia. Thus, she may be in the blast crisis of CML, or have a
de novo acute leukemia. In de novo acute leukemia, the breakpoint in the BCR
gene is often different, producing a fusion gene encoding a p190 protein.
4.
If a molecular analysis were to be done, which laboratory procedures should be
used and what specimen should be obtained?
The RT-PCR analysis should be done of BCR/ABL should be done.
Alternatively, the Southern blot procedure can be performed to detect a
rearranged BCR gene. A bone marrow specimen or peripheral blood specimen
may be used.
5.
The molecular analysis revealed a BCR/ABL translocation consistent with a
breakpoint that results in a p290 protein. What is the diagnosis?
The diagnosis is CML in blast crisis.
6.
Why is this molecular finding helpful in therapy decisions?
The treatment for CML is different from that for an acute leukemia.
7.
Discuss the newest recommended treatment for this condition.
Gleevac is the new treatment of choice. This drug selectively inhibits the
BCR/ABL kinase at submicromolar concentrations. It kills or inhibits the
proliferation of all BCR/ABL expressing cell lines.