| Session: Chronic myelogenous leukemia |
| Case number: 211 |
Submitter(s): Shi-Ping Jiang, Karine Hovanes, Dennis P. O'Malley, Richard McMasters, Wayne Chen, Jess Savala, Michele K. Hibbard.
Clinical history
A 57 year old male with chronic myelogenous leukemia, which showed a variant translocation [t(5;9;22)] at the initial evaluation, re-evaluate after treatment with Gleevec.
Details of gross/microscopic pathology:
Peripheral blood counts were normal. There were no increase in eosinophils, basophils and blasts on the smear. Bone marrow was hypocellular with unremarkable granulopoiesis and erythropoiesis. However, mild dysthrombopoiesis with scattered small hypolobated megakaryocytes was noted, suggestive of residual disease of CML (figure 1). A previous bone marrow (three months ago) showed features characteristic for CML (figure 2).
Immunophenotype (flow cytometry/immunohistochemistry):
Immunophenotyping by flow cytometry detetcted mild dysmaturation of the myeloid cells and no increase in blasts or basophils. A previous immunophenotyping by flow cytometry showed myeloid preonderance with left shifted and dyspoietic maturation (figure 3).
Cytogenetics:
Previous cytogenetic evaluation revealed a simple variant BCR-ABL translocation involving chromosome 5 as the third partner, 46,XY,t(5;9;22)(q35;q34;q11.2)[20]. The cytogenetic evaluation of the current sample revealed two cell lines. The first cell line, seen in 13 of 20 cells, contained the variant translocation previously seen, and the second cell line, seen in 7 of 20 cells, contained a translocation between the long arms of chromosomes 11 and 22, also resulting in what appeared to be a Philadelphia chromosome. A dual fusion translocation BCR/ABL probe set utilized on metaphase chromosomes showed a typical variant translocation pattern containing two orange ABL signals, two green BCR signals, and a BCR/ABL fusion signal in the cell line containing t(5;9;22). However, the fusion signal was on the 11q and not on the 22q (figures 4, 5). Moreover the t(11;22) cell line showed a normal signal pattern of two orange and two green and no fusion signal with the BCR probe on the 11q instead of 22q (figures 6, 7).
Molecular analysis:
RT-PCR assay for BCR/ABL was positive on both previous and current specimens.
Interesting feature(s) of submitted case:
Based on the cytogenetic findings, the possibility of two variant translocations, one involving the (5;9;22) and the other (9;22;11), was entertained. However, three way translocations are thought to occur as a one-step process; therefore, the presence of the second cell line as a result of an independent event seemed unlikely.
Considering the clinical history of this patient, we propose that the patient's constitutional karyotype is the common reciprocal translocation of (11;22) and the BCR/ABL translocation occurred between chromosomes 9 and the derivative 11 in this patient resulting in the presence of the Philadelphia chromosome on 11q. This would explain the absence of the t(11;22) at the emergence of the disease and its presence after therapy.
Proposed diagnosis:
Residual disease of chronic myelogenous leukemia with variant translocation.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Images:
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