Two Cases of Philadelphia Chromosome-negative Essential Thrombocythemia Manifested bcr-abl Gene Rearrangement / 대한임상병리학회지

Discrepant results have been reported in terms of detecting bcr-abl transcripts in patients with essential thrombocythemia that are Philadelphia (Ph) chromosome-negative. We present two cases of Ph chromosome-negative essential thrombocythemia in whom bcr-abl gene rearrangement was detected. In the diagnosis of both cases, they lacked the splenomegaly, anemia and basophilia, and had high platelet counts (948X10(3)/L and 1,329X10(3)/microL, respectively) and normal leukocyte alkaline phosphatase (LAP) scores on admission without any evidence of inflammation, infection, or therapy. They lacked the Philadelphia chromosome characteristic of classical chronic myelogenous leukemia (CML) and had b3a2 transcripts.

Hematological Significance of RT-PCR Test for bcr-abl Rearrangement and the Breakpoint Distribution within the Major bcr in Chronic Myelogenous Leukemia Patients / 대한혈액학회지

BACKGROUND: Bcr-abl rearrangement is the molecular hallmark of chronic myelogenous leukemia (CML). The test for bcr-abl rearrangement, especially using RT-PCR, is the standard test for the diagnosis of CML. We analyzed hematological significances of bcr-abl rearrangement by RT-PCR and the breakpoint distribution within the major bcr in CML patients. METHODS: From 1994 October to 1997 September, we performed the bcr-abl rearrangement using RT-PCR, in 268 untreated patients with various hematologic diseases, and classified the breakpoints within BCR gene as three types (b2a2, b3a2, e1a2) according to PCR product sizes. We compared hematologic parameters between two groups of b2a2 and b3a2 breakpoints in CML. RESULTS: Among the patients with clinically diagnosed CML, 96.8% (61/63) were bcr-abl positive. In ALL, 52.8% (19/36) were bcr- abl positive. All patients with hematologic diseases other than CML or ALL were bcr- abl negative. Among 61 CML patients with positive bcr-abl rearrangement, 19 patients (31.1%) showed b2a2 type and 42 patients (68.9%) b3a2 type. Patients with b3a2 breakpoints showed more frequent peripheral basophilia (P<0.01) than those with b2a2 type. However, other hematologic parameters were not statistically significant. CONCLUSION: RT-PCR test for bcr-abl rearrangement is a specific and efficient test for the diagnosis of CML. However, the hematological significance of b2a2 and b3a2 types is uncertain in CML.

The incidence of ABL Deletion on Derivative 9 Chromosome in Chronic Myelogenous Leukemia by Interphase Fluorescence In Situ Hybridization and its Association with Progression to Blast Crisis / 대한임상병리학회지

BACKGROUND: Philadelphia(Ph) chromosome is found in about 95 percent of chronic myelogenous leukemia(CML) patients. Ph chromosome results from a reciprocal translocation between the long arms of chromosomes 9 and 22, and the fusion gene, BCR-ABL contribute to oncogenesis. Three to five years after first diagnosis, CML progresses to the blast crisis, and is accompanied by secondary cytogenetic changes in about 85% of cases. In this study, we investigated the incidence of ABL deletion of derivative 9 chromosome in CML and evaluated the association between this deletion and progression to the blast crisis by interphase fluorescence in situ hybridization(FISH). METHOD: The subjects included in this study were a consecutive series of 58 patients who were diagnosed as CML at Seoul National University Hospital between January 1997 and April 2000. On 90 archival bone marrow aspirate samples from these 58 CML patients, interphase FISH was performed with a commercially available probe. RESULTS: The ABL deletion of derivative 9 chromosome was detected in 17(29.3%) of 58 patients with CML. Eighteen of 58 patients progressed to blast crisis in this period. ABL deletion was found in 7 of 18 patients with blast crisis, and not in 11 remainders. The mean duration from the diagnosis to blast crisis was 37.1 months in 7 patients with the ABL deletion, while the mean duration was 74.2 months in 11 patients without the ABL deletion. The mean duration from the diagnosis to blast crisis in patients with ABL deletion was significantly shorter than in patients without ABL deletion(P=0.043). CONCLUSIONS: We found that 29.3% of patients with CML had the ABL deletion on derivative 9 chromosome. In these patients, the time taken for evolution to blast crisis was significantly shorter than that of the patients without ABL deletion.