Genomic CDKN2A/2B deletions in adult Ph<sup>+</sup> ALL are adverse despite allogeneic stem cell transplantation.

1. Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Authors
Pfeifer H¹
Markovic S¹
Wunderle L¹
Lang F¹
Hoelzer D¹
Serve H¹
Goekbuget N¹
Ottmann OG¹
(8 authors)
2. Department of Hematology and Oncology and.
Authors
Raum K²
Nowak V²
Fey S²
Obländer J²
Pressler J²
Hofmann WK²
Nowak D²
(7 authors)
3. Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Authors
Böhm V³
Brüggemann M³
(2 authors)
4. Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.
Authors
Hüttmann A⁴
(1 author)
5. Department of Hematology and Oncology, University Hospital Freiburg, Freiburg, Germany.
Authors
Wäsch R⁵
(1 author)

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ORCIDs linked to this article

Blood, 18 Jan 2018, 131(13):1464-1475
https://doi.org/10.1182/blood-2017-07-796862 PMID: 29348129

A comment on this article appears in "ARF way to Ph⁺ ALL stratification?" Blood. 2018 Mar 29;131(13):1394-1395.

Abstract

We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)⁺ acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation (aSCT). Ninety-seven Ph⁺ ALL patients (median age 41 years; range 18-64 years) within the prospective multicenter German Multicenter ALL Study Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with single nucleotide polymorphism arrays and validated by multiplex ligation-dependent probe amplification. The frequencies of recurrently deleted genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6, 5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival (P = .023), disease-free survival (P = .012), and remission duration (P = .036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase 1 and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph⁺ ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT.

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Proteins in UniProt (Showing 5 of 6)

Cyclin-dependent kinase 4 inhibitor B(UniProt - P42772)
p15 protein(UniProt - Q9UM95)
Cyclin-dependent kinase inhibitor(UniProt - Q86WJ4)
Cyclin-dependent kinase inhibitor 2B(UniProt - Q8NIA6)
Cyclin-dependent kinase inhibitor 2B (P15, inhibits CDK4), isoform CRA_b(UniProt - K7PPU3)

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