Browse > Article
http://dx.doi.org/10.7314/APJCP.2016.17.4.1999

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.4, 2016 , pp. 1999-2006 More about this Journal
Abstract
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.
Keywords
APML; cytogenetic response; ATRA; arsenic tri-oxide; peripheral blood; karyotyping;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ghavamzadeh A, Alimoghaddam K, Ghaffari SH, et al (2006). Treatment of acute pro myelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Annals Oncol, 17, 131-4.   DOI
2 Arnould C, Philippe C, Bourdon V, et al (1999). The signal transducer and activator of trans cription STAT5b gene is a new partner of retinoic acid receptor a in acute promyelocyti clike leukemia. Hum Mol Genet, 8, 1741-9.   DOI
3 Arshad A. Pandith, Mushtaq A. Siddiqi (2012). Burden of cancers in the valley of Kashmir 5 year epidemiological reveals a different scenario. Tumor Biol, 33, 1629-37.   DOI
4 Bennett JM, Catovsky D, Daniel MT, et al (1985). Proposed revised criteria for the classifi cation of acute myeloid leukemia: a report of the French-American-British Cooperative Group. Ann Intern Med, 103, 460-2.   DOI
5 Biondi A, Rambaldi A, Pandofi PP, et al (1992). Molecular monitoring of myl/RAR-a fusion gene in acute promyelocytic leukemia by polymerase chain reaction. Blood, 80, 492-7.
6 Borrow J, Goddard AD, Gibbons B, et al (1992). Diagnosis of acute promyelocytic leukae mia by RT-PCR detection of PML-RARA and RAR-PML fusion transcripts. Br J Haematol, 82, 529-40.   DOI
7 Carbone R, Botrugno OA, Ronzoni S, et al (2006). Recruitment ro the histone methyltransfe rase SUB39H1 and its role in the oncogenic properties of the leukemia-associated PML retinoic acid receptor fusion protein. Mol Cell Biol, 26,1288-96.   DOI
8 Cassnat B, Zassadowski F, Balitrand N, et al (2000). Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR. Leukemia, 14, 324-8.   DOI
9 Castaigne S, Chomienne C, Daniel MT, et al (1990). All-trans retinoic acid as a differentia tion therapy for acute promyelocytic leukemia. I. Clinical results. Blood, 76, 1704-9.
10 Chen SJ, Zelent A, Tong JH, et al (1993). Rearrangements of the retinoic acid receptor alpha and promyelocytic zinc finger genes resulting form t(11;17)(q23;q21) in a patient with acute promyelocytic leukaemia. J Clin Invest, 91, 2260-7.   DOI
11 Chen Z, Brand NJ, Chen A, et al(1993). Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-a locus due to a variant t(11; 17) translocation asso-ciated with acute promyelocytic leukaemia. EMBO J, 12, 1161-7.
12 Chomienne C, Ballerini P, Balitrand N et al (1990). All-trans retinoic acid in acute promye locytic leukemias. In vitro studies Structure-function relationship. Blood, 76, 1710-7.
13 David Grimwade, Andrea Biondi, Marie-Joëlle Mozziconacci, et al (2000). Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the euro-pean working party. groupe français de cytogénétique hematologique, groupe de français d'hematologie cellulaire, UK cancer cytogenetics group and BIOMED 1 Eu-ropean community-concerted action "molecular cytogenetic diagnosis in haematolo-gical malignancies. Blood, 96, 1297-308.
14 De Botton S, Chevret S, Sanz M, et al (2000). Additional chromosomal abnormalities in pa-tients with acute promyelocytic leukaemia (APML) do not confer poor prognosis results of APML 93 trial. Br J Haematol, 111, 801-6.
15 Di Croce L, Raker VA, Corsaro M, et al(2002). Methyltransferase recruitment and DNA Hypermethylation of target promoters by an oncogenic transcription factor. Science, 295, 1079-82.   DOI
16 Ghavamzadeh A, Alimoghaddam K, Rostami S, et al (2011). Phase II study of single- agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia. J Clin Oncol, 29, 2753-7.   DOI
17 Dilworth FJ, Chambon P (2000). Nuclear receptors coordinate the activities of chromatin re-modeling complexes and coactivators to facilitate initiation of transcription. Oncogene, 20, 3047-54.
18 Douer D, Santillana S, Ramezani L, et al (2003). Acute promyelocytic leukaemia in patients originating in Latin America is associated with an increased frequency of the bcr1 sub-type of the PML/RARalpha fusion gene. Br J Haematol, 122, 563-570.   DOI
19 Gallagher R, Willman CL, Slack JL, et al (1997). Association of PML/RARa fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: an intergroup molecular study. Blood, 90, 1656-63.
20 Glass CK, Rosenfeld MG (2000). The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev, 14, 121-41.
21 Grimwade D (1999). The pathogenesis of Acute Promyelocytic Leukemia; Evaluation of the role of molecular diagnosis and monitoring in the management of the disease. Br J Hematol, 106, 591-613.   DOI
22 Huang M, Ye YC, Chen BR, et al(1988). Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood, 72, 567-72.
23 Huang W, Sun GL, Li ZS, et al(1993). Acute promyelocytic leukemia: clinical relevance of two major PML-RARa isoforms and detection of minimal residual disease by isoforms and detection of minimal residual disease by retrotrans-criptase/polymerase chain reaction to predict relapse. Blood, 82, 1264-9.
24 Mitelman F (1995). An International System for Humann Cytogenetic Nomenclature. S Karger.
25 Iqbal S, Grimwade D, Chase A, et al (2000). Identification of PML/ RARalpha rearrange ments in suspected acute promyelocytic leukemia using fluorescence in situ hybridization of bone marrow smears: a comparison with cytogenetic and RT-PCR in MRC ATRA trial patients. MRC Adult Leukaemia Working Party. Leukemia, 14, 950-3.   DOI
26 Jensen K, Shiels C, Freement PS (2001). PML protein isoforms and the RBCC/TRIM motif. Oncogene, 20, 7223-33.   DOI
27 Miller WH Jr, Kakizuka A, Frankel SR, et al (1992). Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor-a clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia. Proc Natl Acad Sci USA, 89, 2694-8.   DOI
28 Niyaz A Azad, Shahid M Baba, Zafar A Shah, et al (2015). Phytohemagglutinin-induced pe-ripheral blood cytogenetics: a valid means for diagnosis and imatinib therapy monitoring of chronic phase chronic myeloid leukemia patients. J Cancer Sci Ther, 7, 242-248.
29 Pandolfi PP (2001). In vivo analysis of the molecular genetics of acute promyelocytic leu-kemia. Oncogen, 20, 5726-35.   DOI
30 Pandolfi PP, Alcalay M, Fagioli M, et al (1992). Genomic variability and alternative splicing generate multiple PML/RARa transcripts that encode aberrant PML proteins and PML/RARa isoforms in acute promyelocytic leukemia. EMBO J, 11, 1397-407.
31 Redner RL, Rush EA, Faas S, et al(1996). The t(5;17) variant of acute promyelocytic leu-kemia expresses a nucleophosminretinoic acid receptor fusion. Blood, 87, 882-886.
32 Seabrigth M (1971). A rapid banding technique for human chromosomes. Lancet, 2, 971-72.
33 Vahdat L, Maslak P, Miller WH Jr, et al(1994). Early mortality and retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, lowdose chemotherapy, PML/RAR-a isoform, and CD13 expression in patients treated with all-trans retinoid acid. Blood, 84, 3843-3849.
34 Shen A-X, Chen G-Q, Ni J-H, et al(1997). Use of arsenic trioxide ($AS_2O_3$) in the treatment of acute promyelocytic leukemia (APML): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood, 89, 3354-60.
35 So CC, Wan TS, Chow JL, et al (2011). A single-center cytogenetic study of 629 Chinese patients with de novo acute myeloid leukemia evidence of major ethnic differences and a high prevalence of acute promyelocytic leukemia in Chinese patients. Cancer Genet, 204, 430-8.   DOI
36 van Dongen JJ, Macintyre EA, Gabert JA, et al (1999). Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of mi-nimal residual disease. Report of the BIOMED-1 Concerted Action investigation of mini-mal residual disease in acute leukemia. Leukemia, 13, 1901-28.   DOI
37 Villa R, Morey L, Raker VA, et al (2006). The methyl-CpG binding protein MBD1 is requi-red for PML- RARalpha function. Proc Natl Acad Sci U S A, 103, 1400-5.   DOI
38 Wang AM, Doyle MV, Mont DF (1989). Quantification of mRNA by polymerase chain reac-tion. Proc. Natl Acad Sci USA, 86, 9717-21.   DOI
39 Warrell RP, Frankel SP, Miller WH, et al(1991). Differentiation therapy of acute promyelo-cytic leukemia with tretinoin (all-t"-retinoic acid). N Engl J Med, 324, 1385-9.   DOI
40 Warrell R.P. Jr, de The H, Wang ZY, et al (1993). Acute Promyelocytic leukemia. N Eng J Med, 329, 177-89.   DOI
41 Zhong S, Salomoni P, Pandolfi PP (2000). The transcriptional role of PML and the nuclear body. Nat Cell Biol, 2, 85-90. role of PML and the nuclear body. Nat Cell Biol, 2, 85-90.   DOI
42 Wells RA, Catzavelos C, Kamel-Reid S (1997). Fusion of retinoic acid receptor a to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet, 17,109-113.   DOI