The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia

被引:130
作者
Seifert, H. [1 ]
Mohr, B. [1 ]
Thiede, C. [1 ]
Oelschlaegel, U. [1 ]
Schaekel, U. [1 ]
Illmer, T. [1 ]
Soucek, S. [1 ]
Ehninger, G. [1 ]
Schaich, M. [1 ]
机构
[1] Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, D-01307 Dresden, Germany
关键词
acute myeloid leukemia; p53; deletion; loss of 17p; outcome; prognosis; COMPLEX ABERRANT KARYOTYPE; CHRONIC LYMPHOCYTIC-LEUKEMIA; FLUORESCENCE IN-SITU; GENE-MUTATIONS; CYTOGENETIC ABNORMALITIES; HEMATOLOGIC MALIGNANCIES; MYELOGENOUS LEUKEMIA; BLAST CRISIS; TP53; GENE; EXPRESSION;
D O I
10.1038/leu.2008.375
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Loss of p53-a tumor suppressor gene located on the short arm of chromosome 17 (band 17p13.1)-was detected in 105 out of 2272 (5%) adult acute myeloid leukemia (AML) patients who took part in the Study Alliance Leukemia AML96 and AML2003 multi center trials. There were 85 patients with 17p (p53) deletion with multiple aberrations and 20 patients with a 17p (p53) deletion as single aberration or with only one additional chromosomal abnormality. None of the p53-deleted patients displayed additional low-risk aberrations, like t(8;21) or inv(16). Significant positive association between p53 deletion and other high-risk factors was identified for del(5q) (P<0.001), -5 (P<0.001) and -7 (P<0.05). The molecular risk factors FLT3-ITD and NPM1 mutation showed an inverse correlation to the p53 deletion in complex aberrant patients (P<0.001). The multivariate analysis revealed p53 deletion without multiple aberrations as an independent negative prognostic factor for disease-free survival (P<0.001), relapse risk (P = 0.028) and overall survival (P<0.001). Thus, the single p53 deletion should be considered as a high-risk aberration for future risk-adapted treatment strategies in AML.
引用
收藏
页码:656 / 663
页数:8
相关论文
共 40 条
  • [1] Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:: results from Cancer and Leukemia Group B (CALGB 8461)
    Byrd, JC
    Mrózek, K
    Dodge, RK
    Carroll, AJ
    Edwards, CG
    Arthur, DC
    Pettenati, MJ
    Patil, SR
    Rao, KW
    Watson, MS
    Koduru, PRK
    Moore, JO
    Stone, RM
    Mayer, RJ
    Feldman, EJ
    Davey, FR
    Schiffer, CA
    Larson, RA
    Bloomfield, CD
    [J]. BLOOD, 2002, 100 (13) : 4325 - 4336
  • [2] Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms
    Castro, PD
    Liang, JC
    Nagarajan, L
    [J]. BLOOD, 2000, 95 (06) : 2138 - 2143
  • [3] Coexpression of p53 protein and MDR functional phenotype in leukemias: The predominant association in chronic myeloid leukemia
    Cavalcanti, GB
    Vasconcelos, FD
    de Faria, GP
    Scheiner, MAM
    Dobbin, JD
    Klumb, CE
    Maia, RC
    [J]. CYTOMETRY PART B-CLINICAL CYTOMETRY, 2004, 61B (01) : 1 - 8
  • [4] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia
    Cheson, BD
    Bennett, JM
    Kopecky, KJ
    Büchner, T
    Willman, CL
    Estey, EH
    Schiffer, CA
    Döhner, H
    Tallman, MS
    Lister, TA
    LoCocco, F
    Willemze, R
    Biondi, A
    Hiddemann, W
    Larson, RA
    Löwenberg, B
    Sanz, MA
    Head, DR
    Ohno, R
    Bloomfield, CD
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) : 4642 - 4649
  • [5] Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis
    Christiansen, DH
    Andersen, MK
    Pedersen-Bjergaard, J
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (05) : 1405 - 1413
  • [6] P53 GENE DELETION PREDICTS FOR POOR SURVIVAL AND NONRESPONSE TO THERAPY WITH PURINE ANALOGS IN CHRONIC B-CELL LEUKEMIAS
    DOHNER, H
    FISCHER, K
    BENTZ, M
    HANSEN, K
    BENNER, A
    CABOT, G
    DIEHL, D
    SCHLENK, R
    COY, J
    STILGENBAUER, S
    VOLKMANN, M
    GALLE, PR
    POUSTKA, A
    HUNSTEIN, W
    LICHTER, P
    [J]. BLOOD, 1995, 85 (06) : 1580 - 1589
  • [7] CYTOGENETICS AND THEIR PROGNOSTIC VALUE IN DENOVO ACUTE MYELOID-LEUKEMIA - A REPORT ON 283 CASES
    FENAUX, P
    PREUDHOMME, C
    LAI, JL
    MOREL, P
    BEUSCART, R
    BAUTERS, F
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1989, 73 (01) : 61 - 67
  • [8] FENAUX P, 1992, LEUKEMIA, V6, P246
  • [9] FENAUX P, 1991, BLOOD, V78, P1652
  • [10] Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations
    Fioretos, T
    Strömbeck, B
    Sandberg, T
    Johansson, B
    Billström, R
    Borg, Å
    Nilsson, PG
    Van Den Berghe, H
    Hagemeijer, A
    Mitelman, F
    Höglund, M
    [J]. BLOOD, 1999, 94 (01) : 225 - 232