Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis

被引：118

作者：

Herold, Tobias ^{[1
,2
,3
]}

Schneider, Stephanie ^{[1
]}

Metzeler, Klaus H. ^{[1
,2
,3
]}

Neumann, Martin ^{[1
,2
,3
,4
]}

Hartmann, Luise ^{[1
,2
,3
]}

Roberts, Kathryn G. ^{[5
]}

Konstandin, Nikola P. ^{[1
]}

Greif, Philipp A. ^{[1
,2
,3
]}

Braeundl, Kathrin ^{[1
,2
,3
]}

Ksienzyk, Bianka ^{[1
]}

Huk, Natalia ^{[1
]}

Schneider, Irene ^{[1
]}

Zellmeier, Evelyn ^{[1
]}

Jurinovic, Vindi ^{[6
]}

Mansmann, Ulrich ^{[6
]}

Hiddemann, Wolfgang ^{[1
,2
,3
]}

Mullighan, Charles G. ^{[5
]}

Bohlander, Stefan K. ^{[7
]}

Spiekermann, Karsten ^{[1
,2
,3
]}

Hoelzer, Dieter ^{[8
]}

Bruggemann, Monika ^{[9
]}

Baldus, Claudia D. ^{[2
,3
,4
]}

Dreyling, Martin ^{[1
]}

Goekbuget, Nicola ^{[8
]}

机构：

[1] LMU, Univ Hosp Grosshadern, Dept Internal Med 3, Munich, Germany

[2] German Canc Consortium DKTK, Heidelberg, Germany

[3] German Canc Res Ctr, Heidelberg, Germany

[4] Charite Univ Med Berlin, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany

[5] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA

[6] LMU, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[7] Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand

[8] Goethe Univ Hosp, Dept Med 2, Frankfurt, Germany

[9] Univ Hosp Schleswig Holstein, Dept Hematol, Campus Kiel, Kiel, Germany

来源：

HAEMATOLOGICA | 2017年 / 102卷 / 01期

关键词：

READ ALIGNMENT; EXPRESSION; SIGNATURE; SUBGROUP; CHILDREN; SURVIVAL; DELETION; KINASE; IKZF1; MRD;

D O I：

10.3324/haematol.2015.136366

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was a genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult patients (median age: 42 years) with B-cell precursor ALL (BCP-ALL) were classified as having Ph-like ALL using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002) and mutations in JAK2 (7/16; P<0.001) were found exclusively in the Ph-like ALL subgroup. Clinical and outcome analyses were restricted to patients treated in German Multicenter Study Group for Adult ALL (GMALL) trials 06/99 and 07/03 (n=107). The complete remission rate was 100% among both Ph-like ALL patients (n=19) and the "remaining BCP-ALL" cases (n=40), i.e. patients negative for BCR-ABL1 and KMT2A-rearrangements and the Ph-like subtype. Significantly fewer Ph-like ALL patients reached molecular complete remission (33% versus 79%; P=0.02) and had a lower probability of continuous complete remission (26% versus 60%; P=0.03) and overall survival (22% versus 64%; P=0.006) at 5 years compared to the remaining BCP-ALL patients. The profile of genetic lesions in adults with Ph-like ALL, including older adults, resembles that of pediatric Ph-like ALL and differs from the profile in the remaining BCP-ALL. Our study is the first to demonstrate that Ph-like ALL is associated with inferior outcomes in intensively treated older adult patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed. (NCT00199056, NCT00198991)

引用

页码：130 / 138

页数：9

共 26 条

[1]

[Anonymous], R LANG ENV STAT COMP

[2] BCR-ABL1-like cases in pediatric acute lymphoblastic leukemia: a comparison between DCOG/Erasmus MC and COG/St. Jude signatures [J].

Boer, Judith M. ;

Marchante, Joao R. M. ;

Evans, William E. ;

Horstmann, Martin A. ;

Escherich, Gabriele ;

Pieters, Rob ;

Den Boer, Monique L. .

HAEMATOLOGICA, 2015, 100 (09) :E354-E357

[3] Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1-like subgroup characterized by high non-response and relapse rates [J].

Boer, Judith M. ;

Koenders, Jasper E. ;

van der Holt, Bronno ;

Exalto, Carla ;

Sanders, Mathijs A. ;

Cornelissen, Jan J. ;

Valk, Peter J. M. ;

den Boer, Monique L. ;

Rijneveld, Anita W. .

HAEMATOLOGICA, 2015, 100 (07) :E261-E264

[4] Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008 [J].

Brueggemann, M. ;

Schrauder, A. ;

Raff, T. ;

Pfeifer, H. ;

Dworzak, M. ;

Ottmann, O. G. ;

Asnafi, V. ;

Baruchel, A. ;

Bassan, R. ;

Benoit, Y. ;

Biondi, A. ;

Cave, H. ;

Dombret, H. ;

Fielding, A. K. ;

Foa, R. ;

Goekbuget, N. ;

Goldstone, A. H. ;

Goulden, N. ;

Henze, G. ;

Hoelzer, D. ;

Janka-Schaub, G. E. ;

Macintyre, E. A. ;

Pieters, R. ;

Rambaldi, A. ;

Ribera, J-M ;

Schmiegelow, K. ;

Spinelli, O. ;

Stary, J. ;

von Stackelberg, A. ;

Kneba, M. ;

Schrappe, M. ;

van Dongen, J. J. M. .

LEUKEMIA, 2010, 24 (03) :521-535

[5] 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

[6] Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies [J].

Goekbuget, Nicola ;

Kneba, Michael ;

Raff, Thorsten ;

Trautmann, Heiko ;

Bartram, Claus-Rainer ;

Arnold, Renate ;

Fietkau, Rainer ;

Freund, Mathias ;

Ganser, Arnold ;

Ludwig, Wolf-Dieter ;

Maschmeyer, Georg ;

Rieder, Harald ;

Schwartz, Stefan ;

Serve, Hubert ;

Thiel, Eckhard ;

Brueggemann, Monika ;

Hoelzer, Dieter .

BLOOD, 2012, 120 (09) :1868-1876

[7] Global approach to the diagnosis of leukemia using gene expression profiling [J].

Haferlach, T ;

Kohlmann, A ;

Schnittger, S ;

Dugas, M ;

Hiddemann, W ;

Kern, W ;

Schoch, C .

BLOOD, 2005, 106 (04) :1189-1198

[8] Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group [J].

Haferlach, Torsten ;

Kohlmann, Alexander ;

Wieczorek, Lothar ;

Basso, Giuseppe ;

Kronnie, Geertruy Te ;

Bene, Marie-Christine ;

De Vos, John ;

Hernandez, Jesus M. ;

Hofmann, Wolf-Karsten ;

Mills, Ken I. ;

Gilkes, Amanda ;

Chiaretti, Sabina ;

Shurtleff, Sheila A. ;

Kipps, Thomas J. ;

Rassenti, Laura Z. ;

Yeoh, Allen E. ;

Papenhausen, Peter R. ;

Liu, Wei-min ;

Williams, P. Mickey ;

Foa, Robin .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15) :2529-2537

[9] Development and Validation Of a Highly Sensitive and Specific Gene Expression Classifier To Prospectively Screen and Identify B-Precursor Acute Lymphoblastic Leukemia (ALL) Patients With a Philadelphia Chromosome-Like ("Ph-like" or "BCR-ABL1-Like") Signature For Therapeutic Targeting and Clinical Intervention [J].

Harvey, Richard C. ;

Kang, Huining ;

Roberts, Kathryn G. ;

Chen, I-Ming L. ;

Atlas, Susan R. ;

Bedrick, Edward J. ;

Gastier-Foster, Julie M. ;

Zhang, Jinghui ;

Gerhard, Daniels S. ;

Smith, Malcolm A. ;

Larsen, Eric C. ;

Raetz, Elizabeth A. ;

Winick, Naomi J. ;

Carroll, William L. ;

Stonerock, Eileen ;

Heerema, Nyla A. ;

Carroll, Andrew J. ;

Chen, Shann-Ching ;

Song, Guangchun ;

Becksfort, Jared ;

Rusch, Michael ;

Li, Yongjin ;

Ma, Jing ;

Ell, Denise ;

Reshmi, Shalini C. ;

Loh, Mignon L. ;

Davidas, Meenakshi ;

Hunger, Stephen P. ;

Mullighan, Charles G. ;

Willman, Cheryl L. .

BLOOD, 2013, 122 (21)

[10] An eight-gene expression signature for the prediction of survival and time to treatment in chronic lymphocytic leukemia [J].

Herold, T. ;

Jurinovic, V. ;

Metzeler, K. H. ;

Boulesteix, A-L ;

Bergmann, M. ;

Seiler, T. ;

Mulaw, M. ;

Thoene, S. ;

Dufour, A. ;

Pasalic, Z. ;

Schmidberger, M. ;

Schmidt, M. ;

Schneider, S. ;

Kakadia, P. M. ;

Feuring-Buske, M. ;

Braess, J. ;

Spiekermann, K. ;

Mansmann, U. ;

Hiddemann, W. ;

Buske, C. ;

Bohlander, S. K. .

LEUKEMIA, 2011, 25 (10) :1639-1645

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