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PHA-Induced Peripheral Blood Cytogenetics and Molecular Anslysis : a Valid Diagnostic and Follow-up Modality For Acute Primyelocytic Leukemia Patients Treated With ATRA and/or Arsenic Tri-oxide

  • Baba, Shahid M (Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Azad, Niyaz A (Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Shah, Zaffar A (Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Afroze, Dil (Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Pandith, Arshad A (Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Jan, Aleem (Departement of Clinical Hematology, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Aziz, Sheikh A (Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences) ;
  • Dar, Fayaz A (Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences)
  • 발행 : 2016.06.01

초록

Background: Acute promyelocytic leukemia (APML) is characterized by the reciprocal translocation t(15;17) (p22;p12) resulting in the PML-$RAR{\alpha}$ fusion gene. A dual diagnostic and follow up approach was applied including cytogenetic demonstration of the t(15;17) translocation and detection dg PML-$RAR{\alpha}$ chimeric transcripts by molecular means. Purpose: Conventional cytogenetics involving bone marrow is beset with high probability of poor metaphase index and was substituted with phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis as a diagnostic & follow up modality in APML patients of Kashmir (North India). Both qualitative (RT-PCR) and quantitative (Q-PCR) tests were simultaneously carried out to authenticte the modified cytogenetics. Materials and Method: Patient samples were subjected to the said techniques to establish their baseline as well as follow-up status. Results: Initial cytogenetics revealed 30 patients (81%) Positive for t(15;17) whereas 7 (19%) had either cryptic translocation or were negative for t(15;17). Two cases had chromosome 16q deletion and no hallmark translocation t(15;17). Q-PCR status for PML-$RAR{\alpha}$ was found to be positive for all patients. All the APML patients were reassessed at the end of consolidation phase and during maintenance phase of chemotherapy where 6 patients had molecular relapse, wherein 4 also demonstrated cytogenetic relapse. Conclusions: It was found that PHA-induced peripheral blood cytogenetics along with molecular analysis could prove a reliable modality in the diagnosis and assessment of follow up response of APML patients.

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