Yıl: 2000 Cilt: 17 Sayı: 4 Sayfa Aralığı: 197 - 206 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features

Öz:
BCR/ABL expression, which is the molecular equivalent of the Philadelphia chromosome, is an independent poor risk factor in acute lymphoblastic leukemia (ALL). We used a two-step (nested) reverse transcriptase polimerase chain reaction (RT-PCR) assay to examine BCR/ABL expression in the diagnostic bone marrow specimen of children with ALL, prospectively. Among 75 de novo ALL patients, 4 (%5.3) were found to be BCR/ABL-positive, whereas 4 of 17 relapsed patients (23.5%) were positive.This preliminary study in Turkish children showed an incidence similar to reports from Europe and the U.S.A. More intensive chemotherapies and allogeneic bone marrow transplantations (BMT) during the first remission were planned if a donor was available. Out of 8 BCR/ABL-positive patients, complete remission (CR) was achieved in 7 patients and partial remission (PR) was achieved in 1 patient. Three patients underwent allogeneic BMT during the first CR and 1 under went autologous BMT during the first PR. The Kaplan-Meier estimate o f event-free survival (EFS) of BCR/ABL negative de novo ALL patients was 78.36% at 3 years, whereas the EFS of positive patients was 31.25% at 26 ± 6.4 months. Molecular screening for the Philadelphia chromosome should become a part of the routine diagnostic panel in ALL patients in order to predict which patients have a poor prognosis and need tailored therapy.
Anahtar Kelime: Leukemia, Lymphocytic, Acute Reverse Transcriptase Polymerase Chain Reaction Prospective Studies Diagnostic Techniques and Procedures Philadelphia Chromosome

Konular: Hematoloji
Belge Türü: Makale Makale Türü: Diğer Erişim Türü: Erişime Açık
  • 1. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4- Aminopteroyl-glutamic acid (Aminopterin). New Engl J Med 1948;238:787-91.
  • 2. Kersey JH. Fifty years of studies of the biology and therapy of childhood leukemia. Blood 1997;90: 4243-51.
  • 3. Fletcher JA, Lynch EA, Kimball VM, Donelly M, Tantravahi R, Sallan SE. Translocation (9;22) is associated with exteremly poor prognosis in intensively treated children with acute lymphoblastic leukemia. Blood 1991;77:435-9.
  • 4. Maurer J, Janssen JW, Thiel E, et al. Detection of chimeric BCR/ABL genes in acute lymphoblastic leukemia by the polimerase chain reaction. Lancet 1991; 337:1055-8.
  • 5. Tuszynski A, Dhut S, Young BD, Lister TA, Rohatiner AZ, Amess JA, Chaplin T, Dorey E, Gibbons B. Detection and significance of bcr/abl mRNA transcripts and fusion proteins in Philadelphia positive adult acute lymphoblastic leukemia. Leukemia 1993; 7:1504-8.
  • 6. Kurzrock R, Shalrid M, Romero P, Shtalrid M, Romero P, Kloetzer WS, talpas M, Trujillo JM, Blick M, Beran M, Gutterman JU. A novel c-abl protein product in Philadelphia-positive acute lymphoblastic leukemia. Nature 1987;325:631-5.
  • 7. Chan LC, Karhi KK, Rayter SI, Heisterkamp N, Eridani S, Powles R, Lawler SD, Groffen J, Foulkers J, Greares MF. A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukemia. Nature 1987;325:635-7.
  • 8. Uçkun FM, Nachman JB, Sather HN, Sensel MG, Kraft P, Steinherz PG, Lange B, Hutchinson R, Reaman GH, Gaynon PS, Heerema NA. Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: a report from the Children’s Cancer Group. Cancer 1998;83:2030-9.
  • 9. Sierra J, Radish J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J, Bryant E, Nash RA, Sanders JE, Storb R, Sullivan KM, Appelbaum FR, Anasetti C. Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1997;90:1410-4.
  • 10. Chomezynski P, Sacchi N. Single-Step Method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal Biochem 1987;162:156-9.
  • 11. Gaynon PS, Crotty ML, Sather HN, Bostrom BC, Nachman JB, Steinherz PG, Heerema NA, Sarquis M, Tuel-Ahlgren L, Uçkun FM. Expression of BCR/ABL, E2A-PBX1 and MLL-AF4 fusion transcripts in newly diagnosed children with acute lymphoblastic leukemia. A CCG initiative. Leuk Lymphoma 1997;26:57-65.
  • 12. Priest JR, Robinson WM, Lindquist LL, Warkentin PI, LeBien TW, Woods WG, Kersey JH, Coccia PF, Nesbit ME. Philadelphia chromosome positive childhood acute lymphoblastic leukemia. Blood 1980; 56:15-21.
  • 13. Johansson B, Mertens F, Mitelman F. Geographic Heterogenity of Neoplasia-Associated Chromosome Aberrations. Genes Chromosomes & Cancer 1991;3:1-7.
  • 14. Beyermann B, Agthe AG, Adam H, Seeger K, Linderkamp C, Goetz G, Ludwig W&, Henze G. Clinical features and outcome of children with first marrow relapse of acute lymphoblastic leukemia expressing BCR/ABL fusion transcripts. Blood 1996;87: 1532-8.
  • 15. Devaraj PE, Foroni L, Kitra Roussos V, Secker Walker LM. Detection of BCR/ABL and E2A-PBX1 fusion genes by RT-PCR in acute lymphoblastic leukemia with failed or normal cytogenetics. Br J Haematol 1995;89:349-55.
  • 16. Schrappe M, Arico M, Harbott, Biondi A, Zimmermann M, Conter V, Reiter A, Valsecchi MG, Gadner H, Basso G, Bartram CR, Lampert F, Riehm H, Masera G. Philadelphia Chromosome-Positive (Ph+) Childhood Acute Lymphoblastic Leukemia: Good Initial steroid response allowed early prediction of a favorable treatment outcome. Blood 1988;92: 2730-41.
  • 17. Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Janssen JWG, Ratei R, Schrappe M, Repp R, Zimmermann M, Kabisch H, Janka-Schaub G, Bartram CR, Ludwig WD, Riehm H, Lampert F, Harbott J. Incidence and clinical outcome of children with BCR/ABL- positive acute lymphoblastic leukemia (ALL). A prospective RT/PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM 90 and CoALL-05-92 Leukemia 1996;10:957-63.
  • 18. Crist W, Caroll A, Shuster J, Jackson J, Head D, Borowitz M, Behm F, Link M, Steuber P, Ragab A, Hirt A, Brock B, Land V, Pullen J. Philadelphia chromosome- positive acute leukemia. Clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study. Blood 1990;76:489-94
  • 19. Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, Morilla R, Secker-Walker L, Catovsky D. Cytogenetic findings in acute biphenotypic leukemia. Leukemia 1996;10:1283-7.
  • 20. Baruchel A, Cayuela JM, Ballerini P, LandmannParker J, Cezard V, F›rat H, Haddad E, Aucler MF, Valensi F, Cayrey E, Macintyre EA, Sigaux F. The majority of myeloid antigen positive (My +) childhood B-cell precursor acute lymphoblastic leukemia express TEL-AML 1 fusion transcripts. Br J Hematol 1997; 99:101-6
  • 21. Radish J, Gehly G, Lee A, Avery R, Bryant E, Edmands S, Gooley T, Kessler P, Kirk J, Ladne P, Thomas ED, Appelbaum FR. Detection of bcr/abl transcripts in Philadelphiia chromosome positive acute lymphoblastic leukemia after marrow transplantation. Blood 1997;89:2602-9.
  • 22. Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr/abl oncogene products. Science 1990;247: 1079-82.
  • 23. Kelliher M, Knott A, Mc Laughlin J, Witte ON, Rosenberg N. Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol 1991;11:4710-6.
  • 24. Voncken JW, Kaartinen V, Pattengale PK, Germeraad WTV, Groffen J, Heisterkamp N. BCR/ABL P210 and P190 cause distinct leukemia in transgeneic mice. Blood 1995;86:4603-11.
  • 25. Dunlop LC, Powles R, Singhal S, et al. Bone marrow transplantation for Philadelphia chromosome positive acute lymphoblastic leukemia. Bone Marrow Transplant 1996;17:365-9.
  • 26. Preudhomme C, Henic N, Cazin B, Lai JL, Bertheas MF, Vanrumbeke M, Lemoine F, Jouet JP, Deconninck E, Nelken B, Cosson A, Fennaux P. Good correlation between RT-PCR anlysis and relapse in Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL). Leukemia 1997;11:294-8.
  • 27. Beyermann B, Adams HP, Henze G. Philadelphia chromosome in relapsed childhood leukemia: A matched-pair analysis. Berlin-Frankfurt-Munster Study Group. J Clin Oncol 1997;15:2231-7.
  • 28. Uçkun FM, Nachman JB, Sather HN, et al. Poor treatment outcome of Philadelphia chromosomepositive pediatric acute lymphoblastic leukemia despite intensive chemotherapy. Leuk Lymphoma 1999; 33:101-6.
APA Sarper N, ÖZBEK U, AĞAOĞLU L, OZGEN Ü, Kandilci A, SIRMA S, Anak S, YALMAN N, ERYILMAZ E, DEVECİOĞLU Ö, GEDİKOĞLU G (2000). Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. , 197 - 206.
Chicago Sarper Nazan,ÖZBEK Uğur,AĞAOĞLU Leyla,OZGEN ÜNSAL,Kandilci Ayten,SIRMA Sema,Anak Seniye Sema,YALMAN Nevin,ERYILMAZ Ertuğrul,DEVECİOĞLU Ömer,GEDİKOĞLU Gündüz Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. (2000): 197 - 206.
MLA Sarper Nazan,ÖZBEK Uğur,AĞAOĞLU Leyla,OZGEN ÜNSAL,Kandilci Ayten,SIRMA Sema,Anak Seniye Sema,YALMAN Nevin,ERYILMAZ Ertuğrul,DEVECİOĞLU Ömer,GEDİKOĞLU Gündüz Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. , 2000, ss.197 - 206.
AMA Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. . 2000; 197 - 206.
Vancouver Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. . 2000; 197 - 206.
IEEE Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G "Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features." , ss.197 - 206, 2000.
ISNAD Sarper, Nazan vd. "Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features". (2000), 197-206.
APA Sarper N, ÖZBEK U, AĞAOĞLU L, OZGEN Ü, Kandilci A, SIRMA S, Anak S, YALMAN N, ERYILMAZ E, DEVECİOĞLU Ö, GEDİKOĞLU G (2000). Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. Turkish Journal of Hematology, 17(4), 197 - 206.
Chicago Sarper Nazan,ÖZBEK Uğur,AĞAOĞLU Leyla,OZGEN ÜNSAL,Kandilci Ayten,SIRMA Sema,Anak Seniye Sema,YALMAN Nevin,ERYILMAZ Ertuğrul,DEVECİOĞLU Ömer,GEDİKOĞLU Gündüz Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. Turkish Journal of Hematology 17, no.4 (2000): 197 - 206.
MLA Sarper Nazan,ÖZBEK Uğur,AĞAOĞLU Leyla,OZGEN ÜNSAL,Kandilci Ayten,SIRMA Sema,Anak Seniye Sema,YALMAN Nevin,ERYILMAZ Ertuğrul,DEVECİOĞLU Ömer,GEDİKOĞLU Gündüz Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. Turkish Journal of Hematology, vol.17, no.4, 2000, ss.197 - 206.
AMA Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. Turkish Journal of Hematology. 2000; 17(4): 197 - 206.
Vancouver Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features. Turkish Journal of Hematology. 2000; 17(4): 197 - 206.
IEEE Sarper N,ÖZBEK U,AĞAOĞLU L,OZGEN Ü,Kandilci A,SIRMA S,Anak S,YALMAN N,ERYILMAZ E,DEVECİOĞLU Ö,GEDİKOĞLU G "Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features." Turkish Journal of Hematology, 17, ss.197 - 206, 2000.
ISNAD Sarper, Nazan vd. "Detection of BCR / ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute lymphoblastic leukemia: Incidence and clinical features". Turkish Journal of Hematology 17/4 (2000), 197-206.