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Annals of Hematology

, Volume 92, Issue 6, pp 747–758 | Cite as

Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization

  • Sandra Heesch
  • Martin Neumann
  • Stefan Schwartz
  • Isabelle Bartram
  • Cornelia Schlee
  • Thomas Burmeister
  • Matthias Hänel
  • Arnold Ganser
  • Michael Heuser
  • Clemens-Martin Wendtner
  • Wolfgang E. Berdel
  • Nicola Gökbuget
  • Dieter Hoelzer
  • Wolf-Karsten Hofmann
  • Eckhard Thiel
  • Claudia D. Baldus
Original Article

Abstract

Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.

Keywords

Biphentotypic acute leukemia Acute undifferentiated leukemia Molecular characteristics BAALC, IGFBP7 Flow cytometry 

Notes

Acknowledgments

We want to thank Liliana Mochmann for critical reading of the manuscript and Ouidad Benlasfer for excellent technical assistance.

The authors thank the following institutions for kindly providing clinical data: Aachen: Medizinische Klinik IV—Hämatologie und Onkologie (Prof. Dr. med. Tim H. Brümmendorf); Bad Saarow: Klinik für Innere Medizin III Hämatologie, Onkologie und Palliativmedizin—Sarkomzentrum Berlin-Brandenburg (PD Dr. med. Peter Reichardt); Bonn: Medizinische Klinik III für Hämatologie und Onkologie Universitätsklinikum Bonn (Prof. Dr. med. Peter Brossart); Bremen: Klinikum Bremen-Mitte gGmbH Medizinische Klinik I (Prof. Dr. med. Bernd Hertenstein); Cottbus: Carl-Thiem-Klinikum Cottbus, II. Medizinische Klinik (Prof. Dr. med. Hjalmar B. Steinhauer); Duisburg: Med. Klinik II St. Johannes-Hospital (Prof. Dr. med. C. Aul); Düsseldorf: Universitätsklinikum Düsseldorf Klinik für Hämatologie und Onkologie (Prof. Dr. med. Rainer Haas); Essen: Evangelisches Krankenhaus Essen-Werden gGmbH Klinik für Hämatologie, Onkologie und Stammzelltransplantation (PD Dr. med. Peter Reimer); Essen: Zentrum f. Innere Medizin Med. Klinik u. Poliklinik Abt. f. Hämatologie Universität Essen (Prof. Dr. med. Ulrich Dührsen); Frankfurt (Oder): Medizinische Klinik I (Prof. Dr. med. Michael Kiehl); Freiburg: Medizinische Universitätsklinik Abt. Innere Medizin I (Prof. Dr. Dr. h.c. R. Mertelsmann); Göttingen: Medizinische Universitäts-Klinik Abteilung für Hämatologie/Onkologie (Prof. Dr. med. Lorenz Trümper); Hagen: Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital Klinik für Hämatologie und Onkologie (Dr. med. Hans-Walter Lindemann); Hamburg: Asklepios Klinik St. Georg Hämatologische Abteilung (Prof. Dr. med. N. Schmitz); Hamburg: Asklepios Klinik Altona II. Medizinische Abteilung (Dr. med. D. Braumann); Hamm: Med. Klinik Abteilung für Hämatologie-Onkologie Evangelisches Krankenhaus Hamm (Prof. Dr. med. Jörg Schubert); Homburg/Saar: Universitätsklinikum des Saarlandes Klinik für Innere Medizin I—Onkologie, Hämatologie (Prof. Dr. med. Michael Pfreundschuh); Jena: Universitätsklinikum Jena Klinik für Innere Medizin II Abteilung Hämatologie und Internistische Onkologie (Prof. Dr. med. Andreas Hochhaus); Kaiserslautern: Medizinische Klinik I, Westpfalz-Klinikum GmbH, Standort I Kaiserslautern (Prof. Dr. med. Hartmut Link); Karlsruhe: Städt. Klinikum Karlsruhe, Medizinische Klinik III, Schwerpunkt Onkologie, Hämatologie (Prof. Dr. med. Martin Bentz); Kiel: Universitätsklinikum Schleswig-Holstein Campus Kiel, II. Med. Klinik u. Poliklinik (Prof. Dr. Dr. M. Kneba/M. Brüggemann); Magdeburg: Universitätsklinikum Magdeburg A.ö.R Zentrum für Innere Medizin Klinik für Hämatologie/Onkologie (Prof. Dr. med. Th. Fischer); Mainz: III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität (Prof. Dr. med. Matthias Theobald); Meschede: St. Walburga-Krankenhaus Meschede GmbH (PD Dr. med. M. Schwonzen); Minden: Klinikum Minden Abt. Hämatologie/Onkologie (Prof. Dr. med. M. Griesshammer); Nürnberg: Klinikum Nürnberg Nord Medizinische Klinik 5 (Prof. Dr. med. M. Wilhelm); Oldenburg: Klinikum Oldenburg Innere Medizin II (Prof. Dr. med. C.-H. Köhne); Potsdam: Klinikum Ernst von Bergmann Medizinische Klinik (Prof. Dr. med. G. Maschmeyer); Stuttgart: Robert Bosch-Krankenhaus Abt. Hämatologie/Onkologie (Prof. Dr. med. W. Aulitzky); Tübingen: Medizinische Klinik und Poliklinik Abteilung 2 Hämatologie, Onkologie, Immunologie und Rheumatologie Ambulanz (Prof. Dr. med. L. Kanz); Ulm: Medizinische Universitätsklinik Innere Medizin III (Prof. Dr. med. H. Döhner); Wiesbaden: Horst-Schmidt-Kliniken, Innere Medizin III, Hämatologie/Onkologie (Prof. Dr. med. Norbert Frickhofen); Wuppertal: HELIOS Klinikum Wuppertal Med. Klinik 1 (PD Dr. med. A. Raghavachar)

Funding

This study was supported by research funding from the Gutermuth Stiftung and the Deutsche Krebshilfe to C.D.B.

Conflict of interest disclosure

The authors declare no competing financial interests.

Supplementary material

277_2013_1694_MOESM1_ESM.doc (200 kb)
ESM 1 (DOC 200 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sandra Heesch
    • 1
  • Martin Neumann
    • 1
  • Stefan Schwartz
    • 1
  • Isabelle Bartram
    • 1
  • Cornelia Schlee
    • 1
  • Thomas Burmeister
    • 1
  • Matthias Hänel
    • 2
  • Arnold Ganser
    • 3
  • Michael Heuser
    • 3
  • Clemens-Martin Wendtner
    • 4
  • Wolfgang E. Berdel
    • 5
  • Nicola Gökbuget
    • 6
  • Dieter Hoelzer
    • 6
  • Wolf-Karsten Hofmann
    • 7
  • Eckhard Thiel
    • 1
  • Claudia D. Baldus
    • 1
  1. 1.Department of Hematology, Oncology and Tumor ImmunologyCharité University Hospital BerlinBerlinGermany
  2. 2.Department of Internal Medicine IIIKlinikum ChemnitzChemnitzGermany
  3. 3.Department of Hematology, Hemostasis, Oncology and Stem Cell TransplantationMedical SchoolHannoverGermany
  4. 4.Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical MedicineKlinikum SchwabingMunichGermany
  5. 5.Department of Medicine A, Hematology and OncologyUniversity of MünsterMünsterGermany
  6. 6.Department of Hematology and OncologyJohann Wolfgang Goethe UniversityFrankfurt/MainGermany
  7. 7.Department of Hematology and OncologyUniversity MannheimMannheimGermany

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