Abstract
Background: To evaluate prognostic effect of submicroscopic deletions involving breakage and fusion points of the derivative chromosome 9 and 22 in chronic myeloid leukemia in untreated patients and their follow up samples to correlate with disease outcome. Methods: The study included 78 pretreatment (PT) samples from CML patients and 90 follow-up samples, classified as complete responders (CR, n=33), nonresponders (NR, n =54), and partial responder (PR, n=3) depending on the treatment status of the follow-up samples. Karyotype analysis was performed on metaphases obtained through short term cultures of bone marrow and blood. Detection of BCR-ABL fusion gene was performed using dual color dual fusion (D-FISH) translocation probes. Results: BCR-ABL fusion gene detection by D-FISH showed ABL-BCR deletion on derivative 9 in 47.8% of nonresponders which was higher as compared to pretreatment (11%). Mix D-FISH signal pattern was found in around 20% of pretreatment and non-responder samples. Average interval from chronic phase to blast crisis and accelerated phase was respectively 3.5 and 18 months and accelerated to blast crisis was 16.5 months from the time of diagnosis. The follow-up duration of 31 patients responded to therapy was significantly higher (p=0.0001) as compared to 45 patients who did not respond to therapy. Variant D-FISH signal pattern was seen at the time of diagnosis in patient who responded to therapy as well as those patients who did not respond to therapy. Conclusion: This is the first study from India reporting deletion in ABL, BCR, or ABL-BCR on derivative 9 did not correlate with response to therapy.
Highlights
Variant Cancer Biology, Cell Biology Division, D-Fluorescence in situ hybridization (FISH) signal pattern was seen at the time of diagnosis in patient who responded to therapy as well as those patients who Room No-302, The Gujarat Cancer and Research Institute, Asarawa, did not respond to therapy
This is the first study from India reporting deletion in ABL, Breakpoint Cluster Region (BCR), or ABL-BCR on derivative 9 did not correlate with patel.beena@yahoo.com response to therapy
Conventional cytogenetics and D-FISH in patients who did not respond to therapy Table 5 shows Karyotype and D-FISH pattern at the time of diagnosis in 8 patients who did not respond to therapy
Summary
The study included 78 pretreatment (PT) samples from CML patients and 90 follow-up samples, classified as com- 1Cell Biology Division, The Gujarat plete responders (CR, n=33), nonresponders (NR, n =54), and partial responder (PR, n=3) depending on the treatment Cancer & Research Institute, Asarwa, Ahmedabad, India, 2Department of status of the follow-up samples. Karyotype analysis was performed on metaphases obtained through short term cultures of Medical Oncology and Deputy Director bone marrow and blood. Metaphase cells were captured and analyzed using automated karyotyping system consisting of Axioplan universal epifluorescence microscope (Carl Zeiss) and IKAROS software (Metasystems, Germany). Fluorescence in situ hybridization (FISH) Detection of BCR–ABL fusion gene was performed using BCR/ABL D-FISH translocation probe according to the manufacturer’s instructions (Vysis, Downers Grove, Illinois, USA). This probe mixture contained directly labeled SpectrumOrangeTM probe that spanned the ABL locus at 9q34 (“O” denotes Orange labeled ABL gene) and directly labeled SpectrumGreenTM probe that spanned the BCR locus at 22q11.2 (“G” denotes Green labeled BCR gene). Image acquisition was performed either on automated Olympus epifluorescence microscope and Cytovision software (version 3.7, Applied Imaging System) or Carl Zeiss with ISIS software (Metasystems, Germany)
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