Fusi Gen Translocation Ets Leukemia-Acute Myeloid Leukemia 1 (Tel-Aml1) Sebagai Faktor Prognosis pada Leukemia Limfoblastik Akut Anak

Sri Mulatsih, Sunarto Sunarto, Sutaryo Sutaryo

Sari


Fungsi fusi gen TEL-AML1 dalam leukemogenesis adalah mempengaruhi kunci proses pengaturan, termasuk kenaikan proses cell-renewal yang tidak terkontrol, menghentikan proliferasi dan diferensiasi yang menyebabkan resistensi terhadap proses apoptosis. Banyak studi menghasilkan data bahwa prognosis pasien leukemia limfoblastik akut (LLA) dengan fusi gena TEL-AML1 masih kontroversi, khususnya prognosis jangka panjang. Banyak penelitian yang menghubungkan adanya fusi gena ini dengan resistensi terhadap kemoterapi, dan lainnya menggunakan minimal residual disease (MRD) untuk melihat respons terhadap pengobatan. Adanya co-existences gena lain bisa memberikan kontribusi terhadap prognosis pasien LLA dengan fusi gen TEL-AML1. Dibutuhkan lebih banyak studi translasional untuk lebih memahami peran fusi gen dalam klinik. Pengetahuan mendasar mekanisme molekular pada leukemia sangat penting, khususnya dalam penanganan pasien. Pemahaman yang lebih baik tentang patogenesis leukemia bisa menghasilkan pengertian dan pengetahuan baru untuk menyusun strategi baru dalam penanganan pasien LLA yang didasarkan kaidah molekular

Kata Kunci


leukemia limfoblastik akut; TEL-AML1; prognosis

Teks Lengkap:

PDF

Referensi


Pui CH, Sandlud JT, Pei D. Results of therapy for acute lymphoblastic leukemia in black and white children. JAMA 2003;290:2001-7.

Friedman AM, Weinstein HJ, The Role of Prognostic Features in the Treatment of Childhood Acute Lymphoblastic Leukemia. The Oncologist 2000;5:321-328.

Cline, M.J. The molecular basis of leukemia (review article). NEJM 2004;330:328-36.

Cleary ML. Ongogenic conversion of transcription factors by chromosomal translocation. Cell 1991; 66:1-3.

Rubnitz JE, Crist, WM. Molecular genetics of chilhood cancer: Implications for pathogenesis, diagnosis, and treatment. Pediatrics 1997;100:101-08.

Korsmeyer SJ. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Annu Rev Immunol 1992;10:785-807 (Medline).

Pui CH, Evans. Acute lymphoblastic leukemia, Narrator Engl J Med 2004;339:605-15.

Heerema NA, Sather HN, Senselm MG, Uckun FM. Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the children’s cancer group. J of Clin Oncol 1998;16:1270-8.

Seeger K, Adams HP, Buchwald D, Henze G. TEL-AML1 fusion transcript in relapsed childhood acute lymphoblastic leukemia. The Berlin-Frankfurt-Munster Study Group. Blood 1988;91:1716-22.

Diakos C, Krapf G, Gerner C, Gruemayer RP. RNAi-mediated silencing of TEL-AML1 reveals a heat-shock protein–and survivin-dependent mechanism for survival. Blood 2007;109:2607-10.

Brisco MJ, Sykes PJ, Dolman G, Morley AA. Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia [see comments]. Leukemia 1997;11:1497.

Pui CH, Carroll AJ, Raimondi SC, Behm FG. Clinical presentation, karyotypic characterization and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line. Blood 1990;75:1170-7.

Shurtleft SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 1995;9:1985-9.

Whitehead VM, Vuchich MJ, Lauer SJ. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric oncology group study. Blood 1992;80:1316-23.

Zuna. The role of TEL and AML1 genes in the pathogenesis of hematologic malignancies. Cas Lek Cesk 2001;140:131-7.

McLean TW, Ringold S, Neuberg D, Stegmaier K, Tantravahi R, Ritz J. TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood 1996;88:4252-8.

Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L. Incidence and clinical relevance of TEL/AML 1 fusion genes in children with acute lymphoblastic leukemia enrolled in the Germans and Italian multicenter therapy trials. Blood 1997;90: 571-7.

Cayuela JM, Baruchel A, Orange C, Madani A, Auclerc MF, Daniel MT. TEL-AML1 fusion RNA as a new target to detect minimal residual disease in pediatric B-cell precursor acute lymphoblastic leukemia. Blood 1996;88:302.

Stams WAG, Boer ML, Beverloo HB, Pieters R. Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL. Blood, 2003;101:2743-7.

Krejci O, Starkova J, Otova B, Trka J. Upregulation of asparagine synthetase fails to avert cell cycle arrest induced by L-asparaginase in TEL/AML1-positive leukaemic cells. Leukemia 2004;8:434-41.

Stams WAG, Den Boer ML, Holleman A, Pieters R. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1–negative but not TEL-AML1–positive pediatric acute lymphoblastic leukemia. Blood 2005;105:4223-5.

Appel LM, Den Boer ML, Meijerink JPP, Veerman AJP, Reniers NCM, Pieters R. Up-regulation of asparagine synthetase expression is not linked to the clinical response to L-asparaginase in pediatric acute lymphoblastic leukemia. Blood 2006;107:4244-9.

Uckun FM, Pallisgaard N, Hokland P, Heerema N. Expression of TEL-AML1 fusion transcript and response to induction therapy in standar risk acute lymphoblastic leukemia. Leuk Lymphoma 2001;42:41-56.

Madzo J, Zuna J, Muzikova K, Trka J. Slower molecular response to treatment predict poor outcome in patients with TEL/AML1 positive acute lymphoblastic leukemia: prospective real-time quantitative reverse trabscriptase-polymerase chain reaction study. Cancer 2003;97:105-13

Mosad E, Hamed HB, Bakry RM, Ezz-Eldin AM, Khalifa NM. Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study. J Hematol Oncol 2008;1:17

Ma SK, Wan TS, Cheuk AT, Chan LC. Characterization of additional gentic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetic study. Leukemia 2001;15:1442-7.

Mikhail FM, Serry KA, Hatem N, Nucifora G. AML1 gene ever-expression in childhood acute lymphoblastic leukemia. Leukemia 2002;16:658-68.

Rothman R, Trakhtenbrot L, Bielorai B, Toren A. Co-existensi of multiple subclones in TEL-AML1 at diagnosis of acute lymphoblastic leukaemia in association with submicroscopic deletion of AML1. Br J Haematol 2005;129:491-8.

Gandemer V, Rio AG, Tayrac M, Galibert MD. Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia. BMC Genomics 2007;8:385.




DOI: http://dx.doi.org/10.14238/sp10.6.2009.404-9

Refbacks

  • Saat ini tidak ada refbacks.


##submission.copyrightStatement##

##submission.license.cc.by-nc-sa4.footer##

Informasi Editorial:
Badan Penerbit Ikatan Dokter Anak Indonesia
Jl. Salemba I No 5, Jakarta 10430, Indonesia
Phone/Fax: +62-21-3912577
Email: editorial [at] saripediatri.org

Lisensi Creative Commons
Sari Pediatri diterbitkan oleh Badan Penerbit Ikatan Dokter Anak Indonesia
Ciptaan disebarluaskan di bawah Lisensi Creative Commons Atribusi-NonKomersial-BerbagiSerupa 4.0 Internasional.