Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome

被引：319

作者：

Harvey, Richard C. ^{[1
,2
,3
,4
,5
,6
]}

Mullighan, Charles G. ^{[7
,8
]}

Wang, Xuefei ^{[1
,2
,3
,4
,5
]}

Dobbin, Kevin K. ^{[9
]}

Davidson, George S. ^{[10
]}

Bedrick, Edward J. ^{[1
,2
,3
,4
,5
]}

Chen, I-Ming ^{[1
,2
,3
,4
,5
,6
]}

Atlas, Susan R. ^{[1
,2
,3
,4
,5
]}

Kang, Huining ^{[1
,2
,3
,4
,5
]}

Ar, Kerem ^{[1
,2
,3
,4
,5
]}

Wilson, Carla S. ^{[1
,2
,3
,4
,5
]}

Wharton, Walker ^{[1
,2
,3
,4
,5
]}

Murphy, Maurice ^{[1
,2
,3
,4
,5
]}

Devidas, Meenakshi ^{[6
,11
,12
]}

Carroll, Andrew J. ^{[11
,12
,13
]}

Borowitz, Michael J. ^{[6
,14
]}

Bowman, W. Paul ^{[6
,15
]}

Downing, James R. ^{[7
,8
]}

Relling, Mary ^{[7
,8
]}

Yang, Jun ^{[7
,8
]}

Bhojwani, Deepa ^{[7
,8
]}

Carroll, William L. ^{[6
,16
,17
,18
]}

Camitta, Bruce ^{[6
,19
]}

Reaman, Gregory H. ^{[6
,20
]}

Smith, Malcolm ^{[21
]}

Hunger, Stephen P. ^{[6
,22
,23
]}

Willman, Cheryl L. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA

[2] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA

[3] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA

[4] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA

[5] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA

[6] Childrens Oncol Grp, Arcadia, CA USA

[7] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[8] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[9] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA

[10] Sandia Natl Labs, Albuquerque, NM 87185 USA

[11] Univ Florida, Coll Med, Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA

[12] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA

[13] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA

[14] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[15] Cook Childrens Med Ctr, Ft Worth, TX USA

[16] NYU, Med Ctr, Dept Pediat, New York, NY 10016 USA

[17] NYU, Med Ctr, Dept Hematol & Oncol, New York, NY 10016 USA

[18] NYU, Med Ctr, Ctr Canc, New York, NY 10016 USA

[19] Med Coll Wisconsin, Dept Pediat Hematol Oncol & Transplantat, Milwaukee, WI 53226 USA

[20] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA

[21] NCI, Canc Therapy Evaluat Program, Pediat Oncol Branch, Bethesda, MD 20892 USA

[22] Univ Colorado Denver, Sch Med, Univ Colorado Canc Ctr, Aurora, CO USA

[23] Childrens Hosp, Dept Pediat, Aurora, CO USA

来源：

BLOOD | 2010年 / 116卷 / 23期

基金：

美国国家卫生研究院;

关键词：

MINIMAL RESIDUAL DISEASE; ONCOLOGY-GROUP; SURVIVAL; CLASSIFICATION; CHILDREN; CRLF2; PROGENITOR; REARRANGEMENT; PREDICTION; ETHNICITY;

D O I：

10.1182/blood-2009-08-239681

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known recurring cytogenetic abnormalities, we performed gene expression profiling in a cohort of 207 uniformly treated children with high-risk ALL. Expression profiles were correlated with genome-wide DNA copy number abnormalities and clinical and outcome features. Unsupervised clustering of gene expression profiling data revealed 8 unique cluster groups within these high-risk ALL patients, 2 of which were associated with known chromosomal translocations (t(1;19)(TCF3-PBX1) or MLL), and 6 of which lacked any previously known cytogenetic lesion. One unique cluster was characterized by high expression of distinct outlier genes AGAP1, CCNJ, CHST2/7, CLEC12A/B, and PTPRM; ERG DNA deletions; and 4-year relapse-free survival of 94.7% +/- 5.1%, compared with 63.5% +/- 3.7% for the cohort (P = .01). A second cluster, characterized by high expression of BMPR1B, CRLF2, GPR110, and MUC4; frequent deletion of EBF1, IKZF1, RAG1-2, and IL3RA-CSF2RA; JAK mutations and CRLF2 rearrangements (P < .0001); and Hispanic ethnicity (P < .001) had a very poor 4-year relapse-free survival (21.0% +/- 9.5%; P < .001). These studies reveal striking clinical and genetic heterogeneity in high-risk ALL and point to novel genes that may serve as new targets for diagnosis, risk classification, and therapy. (Blood. 2010;116(23):4874-4884)

引用

页码：4874 / 4884

页数：11

共 36 条

[1]

[Anonymous], 2006, R FDN STAT COMP

[2]

Armitage P., 2001, STAT METHODS MED RES, V4th

[3] Statistics review 12: Survival analysis [J].

Bewick, V ;

Cheek, L ;

Ball, J .

CRITICAL CARE, 2004, 8 (05) :389-394

[4] Racial and ethnic differences in survival of children with acute lymphoblastic leukemia [J].

Bhatia, S ;

Sather, HN ;

Heerema, NA ;

Trigg, ME ;

Gaynon, PS ;

Robison, LL .

BLOOD, 2002, 100 (06) :1957-1964

[5] Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's oncology group study on behalf of the Dutch Childhood Oncology Group and the German Cooperative Study Group for childhood acute lymphoblastic leukemia [J].

Bhojwani, Deepa ;

Kang, Huining ;

Menezes, Renee X. ;

Yang, Wenjian ;

Sather, Harland ;

Moskowitz, Naomi P. ;

Min, Dong-Joon ;

Potter, Jeffrey W. ;

Harvey, Richard ;

Hunger, Stephen P. ;

Seibel, Nita ;

Raetz, Elizabeth A. ;

Pieters, Rob ;

Horstmann, Martin A. ;

Relling, Mary V. ;

den Boer, Monique L. ;

Willman, Cheryl L. ;

Carroll, William L. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (27) :4376-4384

[6] The logrank test [J].

Bland, JM ;

Altman, DG .

BRITISH MEDICAL JOURNAL, 2004, 328 (7447) :1073-1073

[7] Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study [J].

Borowitz, Michael J. ;

Devidas, Meenakshi ;

Hunger, Stephen P. ;

Bowman, W. Paul ;

Carroll, Andrew J. ;

Carroll, William L. ;

Linda, Stephen ;

Martin, Paul L. ;

Pullen, D. Jeanette ;

Viswanatha, David ;

Willman, Cheryl L. ;

Winick, Naomi ;

Camitta, Bruce M. .

BLOOD, 2008, 111 (12) :5477-5485

[8] Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study [J].

Borowitz, MJ ;

Pullen, DJ ;

Shuster, JJ ;

Viswanatha, D ;

Montgomery, K ;

Willman, CL ;

Camitta, B .

LEUKEMIA, 2003, 17 (08) :1566-1572

[9] A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study [J].

Den Boer, Monique L. ;

van Slegtenhorst, Marjon ;

De Menezes, Renee X. ;

Cheok, Meyling H. ;

Buijs-Gladdines, Jessica G. C. A. M. ;

Peters, Susan T. C. J. M. ;

Van Zutven, Laura C. M. ;

Beverloo, H. Berna ;

Van der Spek, Peter J. ;

Escherich, Gaby ;

Horstmann, Martin A. ;

Janka-Schoub, Gritta E. ;

Kamps, Willem A. ;

Evans, William E. ;

Pieters, Rob .

LANCET ONCOLOGY, 2009, 10 (02) :125-134

[10] Cluster analysis and display of genome-wide expression patterns [J].

Eisen, MB ;

Spellman, PT ;

Brown, PO ;

Botstein, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868

← 1 2 3 4 →