Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients

Haematologica

Volumn 95, Issue 5, 2010, Pages 745-751

  Chillón, Maríla Carmen ^a   Santamaría, Carlos ^a,b   García Sanz, Ramón ^a,b   Balanzategui, Ana ^a   Sarasquete, María Eugenia ^a   Alcoceba, Miguel ^a   Marín, Luis ^a   Caballero, María Dolores ^a   Vidriales, María Belén ^a   Ramos, Fernando ^c   Bernal, Teresa ^d   Díaz Mediavilla, Joaquín ^e   de Coca, Alfonso García ^f   Peñarrubia, María Jesús ^g   Queizán, José Antonio ^h   Giraldo, Pilar ⁱ   Miguel, Jesús F San ^a,b   González, Marcos ^a,b  

^a HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^b Centro de Investigacion del Cancer   (Spain)

^c UNIVERSITY OF LEÓN   (Spain)

^d HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS   (Spain)

^e HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^f HOSPITAL CLÍNICO UNIVERSITARIO DE VALLADOLID   (Spain)

^g HOSPITAL UNIVERSITARIO RÍO HORTEGA   (Spain)

^h HOSPITAL GENERAL DE SEGOVIA   (Spain)

ⁱ HOSPITAL UNIVERSITARIO MIGUEL SERVET   (Spain)

Author keywords

Acute promyelocytic leukemia; Flt3 itd size; Pml rara level; Prognosis

Indexed keywords

CD135 ANTIGEN; PROMYELOCYTIC LEUKEMIA PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PML RAR ALPHA; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BLAST CELL; CONTROLLED STUDY; FEMALE; GENE DUPLICATION; GENE EXPRESSION; GENE MUTATION; GENE NUMBER; HUMAN; IMMUNOPHENOTYPING; LEUKOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; OVERALL SURVIVAL; POINT MUTATION; PROGNOSIS; PROMYELOCYTIC LEUKEMIA; PROTEIN BLOOD LEVEL; SURVIVAL RATE;

ADULT; COHORT STUDIES; FEMALE; FMS-LIKE TYROSINE KINASE 3; FOLLOW-UP STUDIES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LEUKEMIA, PROMYELOCYTIC, ACUTE; MALE; MIDDLE AGED; ONCOGENE PROTEINS, FUSION; POINT MUTATION; RISK FACTORS; TANDEM REPEAT SEQUENCES; TUMOR MARKERS, BIOLOGICAL; YOUNG ADULT;

EID: 77952304009     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2009.015073     Document Type: Article

References (38)

1. Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100(3):4372-80.
2. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100(1):59-66.
3. Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99(12):4326-35.
4. Chillon MC, Fernandez C, Garcia-Sanz R, Balanzategui A, Ramos F, Fernandez-Calvo J, et al. FLT3-activating mutations are associated with poor prognostic features in AML at diagnosis but they are not an independent prognostic factor. Hematol J. 2004; 5(3):239-46
5. Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111(5):2776-84.
6. Callens C, Chevret S, Cayuela JM, Cassinat B, Raffoux E, de Botton S, et al. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group. Leukemia. 2005;19(7):1153-60.
7. Gale RE, Hills R, Pizzey AR, Kottaridis PD, Swirsky D, Gilkes AF, et al. Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood. 2005;106(12):3768-76.
8. Kuchenbauer F, Schoch C, Kern W, Hiddemann W, Haferlach T, Schnittger S. Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia. Br J Haematol. 2005;130(2):196-202.
9. Mathews V, Thomas M, Srivastava VM, George B, Srivastava A, Chandy M. Impact of FLT3 mutations and secondary cytogewith newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen. Haematologica. 2007;92(7):994-5.
10. Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001;61(19):7233-9.
11. Baldus CD, Thiede C, Soucek S, Bloomfield CD, Thiel E, Ehninger G. BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications. J Clin Oncol. 2006;24(5):790-7.
12. Stirewalt DL, Kopecky KJ, Meshinchi S, Engel JH, Pogosova-Agadjanyan EL, Linsley J, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107(9):3724-6.
13. Ponziani V, Gianfaldoni G, Mannelli F, Leoni F, Ciolli S, Guglielmelli P, et al. The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia. 2006;20(11): 2074-6.
14. Mistry AR, Pedersen EW, Solomon E, Grimwade D. The molecular pathogenesis of acute promyelocytic leukaemia: implications for the clinical management of the disease. Blood Rev. 2003;17(2):71-97.
15. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999; 93(12):4131-43.
16. Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998;16(1):78-85.
17. Ades L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008;111(3):1078-84.
18. Sanz MA, Lo CF, Martin G, Avvisati G, Rayon C, Barbui T, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96(4):1247-53.
19. Gallagher RE, Yeap BY, Bi W, Livak KJ, Beaubier N, Rao S, et al. Quantitative real- time RT-PCR analysis of PML-RAR alpha mRNA in acute promyelocytic leukemia: assessment of prognostic significance in adult patients from intergroup protocol 0129. Blood. 2003;101(7):2521-28.
20. Schnittger S, Weisser M, Schoch C, Hiddemann W, Haferlach T, Kern W. New score predicting for prognosis in PML- RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts. Blood. 2003;102(8):2746-55.
21. Gabert J, Beillard E, van der Velden VH, Bi W, Grimwade D, Pallisgaard N, et al. Standardization and quality control studies of 'real-time' quantitative reverse transcrip5)tase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program. Leukemia. 2003;17(12):2318-57.
22. Yoo SJ, Chi HS, Jang S, Seo EJ, Seo JJ, Lee JH, et al. Quantification of AML1-ETO fusion transcript as a prognostic indicator in acute myeloid leukemia. Haematologica. 2005;90(11):1493-501.
23. Krauter J, Gorlich K, Ottmann O, Lubbert M, Dohner H, Heit W, et al. Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias. J Clin Oncol. 2003;21(23):4413-22.
24. Marcucci G, Caligiuri MA, Dohner H, Archer KJ, Schlenk RF, Dohner K, et al. Quantification of CBFbeta/MYH11 fusion transcript by real time RT-PCR in patients with INV(16) acute myeloid leukemia. Leukemia. 2001;15(7):1072-80.
25. Sanz MA, Martin G, Rayon C, Esteve J, Gonzalez M, az-Mediavilla J, et al. A modified AIDA protocol with anthracycline- based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHE- MA group. Blood. 1999;94(9):3015-21.
26. Sanz MA, Martin G, Gonzalez M, Leon A, Rayon C, Rivas C, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004; 103(4):1237-43.
27. Orfao A, Chillon MC, Bortoluci AM, Lopez-Berges MC, Garcia-Sanz R, Gonzalez M, et al. The flow cytometric pattern of CD34, CD15 and CD13 expression in acute myeloblastic leukemia is highly characteristic of the presence of PML- RARalpha gene rearrangements. Haematologica. 1999;84(5):405-12.
28. Santamaria C, Chillon MC, Fernandez C, Martin-Jimenez P, Balanzategui A, Garcia SR, et al. Using quantification of the PML- RARalpha transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia. Haematologica. 2007;92(3): 315-22.
29. Beillard E, Pallisgaard N, van der Velden VH, Bi W, Dee R, van der Schoot E, et al. Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using 'real-time' quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program. Leukemia. 2003;17(12): 2474-86.
30. Kaplan EL, Meier P. Nonparametric estimations from incomplete observations. J Am Stat Assoc. 1958;53:457-81.
31. Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1(11):710-9.
32. Cox DR. Regression models and life tables (with discussion). J Royal Stat Soc. 1972; 34:187-220.
33. Santamaria C, Chillon MC, Garcia-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M, et al. The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia. Haematologica. 2008;93(12):1797-805.
34. Noguera NI, Breccia M, Divona M, Diverio D, Costa V, De Santin S, et al. Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia. 2002;16(11):2185-9.
35. Shih LY, Kuo MC, Liang DC, Huang CF, Lin TL, Wu JH, et al. Internal tandem duplication and Asp835 mutations of the FMS-like tyrosine kinase 3 (FLT3) gene in acute promyelocytic leukemia. Cancer. 2003; 98(6):1206-16.
36. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100(5):1532-42.
37. Westervelt P, Lane AA, Pollock JL, Oldfather K, Holt MS, Zimonjic DB, et al. High-penetrance mouse model of acute promyelocytic leukemia with very low lev-els of PML-RARalpha expression. Blood. 2003;102(5): 1857-65.
38. Albano F, Mestice A, Pannunzio A, Lanza F, Martino B, Pastore D, et al. The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. Haematologica 2006; 91(3):311-6.