【正文】 腫瘤最常用的基礎性化療藥物之一，能有效誘導淋巴白血病細胞凋亡。臨床上，潑尼松敏感試驗結果已被公認為判斷ALL細胞生物學行為、早期治療反應、調整臨床危險度和預測預后的重要指標。為此，我們專門統(tǒng)計分析了潑尼松敏感和潑尼松不敏感ALL組IK表達情況，結果發(fā)現潑尼松不敏感ALL組(22%)功能性IK陽性表達率顯著低于潑尼松敏感組(71%) (P)。這一研究結果表明，功能性IK表達異常從一定程度上反映了淋巴白血病細胞的生物學行為，有可能成為一個預測ALL患者糖皮質激素耐藥、早期治療反應和遠期預后的重要指標，很值得深入研究。全文總結本文采用巢式RTPCR技術結合DNA測序，在國內首次研究了IK在兒童ALL的表達情況，及其不同預后因素ALL組間功能性和顯性負IK轉錄本陽性表達率，初步探討了IK表達情況與兒童ALL臨床危險預后因素的關系。結果發(fā)現：(1) ALL患兒和正常對照兒童總的IK表達譜具有顯著差異。正常兒童幾乎均表達功能性IK轉錄本，而多數ALL患兒表達顯性負IK，且部分病例甚至僅高水平表達一種或多種“顯性負”IK；(2) ALL患兒功能性性IK陽性表達率顯著低于對照兒童；(3) 具有某些不良預后因素(如高危組和潑尼松不敏感)的ALL患兒，功能性IK陽性表達率明顯低于相應的良好預后因素ALL組。本研究由于研究經費和RTPCR技術本身的局限性，經統(tǒng)計學分析未能得出我國ALL患兒顯性負IK陽性表達率也顯著增高這個預期的研究結果，但卻發(fā)現ALL患兒功能性IK陽性表達率顯著低于對照兒童。更為重要的是，我們研究發(fā)現具有某些公認與淋巴白血病細胞本身生物學行為和ALL預后密切相關的不良危險因素的ALL，其功能性IK轉錄本陽性表達率顯著降低，從另一個方面證實了IK在兒童ALL發(fā)病中發(fā)揮著重要作用，IK異常表達(功能性IK表達降低和或顯性負IK表達增高)可能是某些具有高危不良預后因素ALL的一個普遍分子生物學特征，很值得進一步深入研究。參考文獻1. Silverman LB, Stevenson KE, O’Brien JE, et al. Longterm results of DanaFarber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia(19852000). Leukemia. 2010:24(2):320334.2. Conter V, Arico M, Basso G, et al. Longterm results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia. Leukemia. 2010:24(2):255264.3. Gaynon PS,Angiolillo AL, Carroll WL,et al. Longterm results of the children’s cancer group studies for childhood acute lymphoblastic leukemia 19832002: a Children’s Oncology Group Report. :24(2):285297.4. Moricke A, Zimmermann M, Reiter A, et al. Longterm results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALLBFM study group from 19812000. Leukemia. 2010。24(2):265284.5. Cea M, Cagnetta A, Garuti A, et al. Molecular diagnosis and monitoring of chronic myelogenous leukemia: BCRAbl and more. J BUON. 2009。14:56573.6. Stam RW, den Boer ML, Passier MM, et al. Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant acute lymphoblastic leukemia. Leukemia. 2006。20:246271.7. O’Nell J, Look AT. Mechanisms of transcription deregulation in lymphoid cell transformation. Oncogeen. 2007。26:68386849.8. Georgopoulos K, Moore DD,Derfler B. Ikaros, an early lymphoidsepcific transcription factor and a putative mediator for T cell mitment. Science. 1992。258:808812.9. Molnar A, Wu P, Largespada DA, et al. The Ikaros gene encodes a family of lymphocyterestricted zinc finger DNA binding proteins, highly conserved in human and mouse. J Immunol. 1996。156(2):585592.10. Nera KP, Alinikula J, Terho P, et al. Ikaros has a crucial role in regulation of B cell receptor signaling. Eur J Immunol. 2006。36:516–525.11. Molnar A, Wu P, Largespada DA, et al. The Ikaros gene encodes a family of lymphocyterestricted zinc finger DNA binding proteins, highly conserved in human and mouse. J. Immun. 1996。156: 585592.12. Nietfeld W, Meyerhans A. Cloning and sequencing of hIK1, a cDNA encoding a human homologue of mouse Ikaros/LyF1. Immunol Lett. 1996。49:134141.13. Georgopoulos K, Bigby M, Wang JH, et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell. 1994。79:143156.14. Rebolo A, Schmitt C. Ikaros, Aiolos and Helios: transcription regulator and lymphoid malignancies. Immunol Cell Biol. 2003。81:171185.15. Sun L, Crotty ML, Sensel M, et al. Expression of dominantnegative isoforms in Tcell acute lymphoblastic leukemia. Clin Cancer Res. 1999。5:21122120.16. Nakase K, Ishimaru F, Avitahl N, et al. Dominant negative isoform of the Ikaros gene in patients with adult Bcell acute lymphoblastic leukemia. Cancer Res. 2000。60:40624065.17. Sun L, Crotty ML, Sensel M, et al. Expression of dominantnegative isoforms in Tcell acute lymphoblastic leukemia. Clin Cancer Res. 1999。5:21122120.18. Yagi T, Hibi S, Takanshi M, et al. High frequency of Ikaros isoform 6 expression in acute myelomonocytic and monocytic leukemias: implications for upregulation of the antiapoptotic protein BclXL in leukemogenesis. Blood. 2002。99:13501355.19. Winandy S, Wu P, Georgopoulos K. A dominant mutation in the Ikaros gene leads to rapid development of leukemia and lymphoma. Cell. 1995。83:289299.20. Levine RL. Inherited susceptibility to pediatric ALL. Nature Genet. 2009。41(9):957958.21. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. New Engl J Med. 2009。360:470480.22. Papaemmanuil E, Hosking FJ, Vijayakrishnan J, et al. Loci on , and are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet. 2009。41:10061011.23. Sun L, Heerema N, Crotty L, et al. Expression of dominantnegative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia. PNAS. 1999。96:680685.24. Iacobucci I, Lonetti A, Messa F, et al. Expression of spliced oncogenic Ikaros isoforms in Philadelphiapositive acute lymphoblastic leukemia patients treated with tyrosine kinase inhibitors:implications for a new mechanism of resistance. Blood. 2008。112:38473855.25. Martinelli G, Iacobucci I, Tiziana C, et al. IKZF1(Ikaros) deletions in BCRABL1positive acute lymphoblastic leukemia are associated with short diseasefreee survival and high rate of cumulative incidence of relapse: A GIMEMA AL WP Report. J Clin Oncol. 2009。27:52025207.26. Iacobucci I, Storlazzi CT, Gilloni D, et al. Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCRABL1positive ALL patientson behalf of CIMEMA AL WP. Blood。2009。114(10):21592167.27. 孫媛媛, 柴曄, 張連生, 等. B系急性淋巴細胞白血病患者Ikaros基因改變及其在臨床預后評價中的意義. 2009。第三屆中國腫瘤內科大會教育集暨論文集. 28. Iacobucci I, Lonetti A, Messa F, et al. Expression of spliced oncogenic Ikaros isoforms in Ph+ALL patients treated with tyrosine kinase inhibitorsimplications for a new mechanism of resistance. Blood. 2008。112:38473855.29. Tonnelle C, Dijon M, Moreau T,