Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Acute Leukemias

GAS6 expression identifies high-risk adult AML patients: potential implications for therapy

Leukemia volume 28, pages 1252–1258 (2014)Cite this article

Subjects

Abstract

Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged<60 years; n=199 aged ⩾60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged ⩾60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6−). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+ patients included overexpressed BAALC and MN1, known to confer adverse prognosis in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and its receptor genes, chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. This study reports for the first time that GAS6 expression is an adverse prognostic marker in CN-AML. Although GAS6 decoy receptors are not yet available in the clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+-associated pathways, for example, CXCR4 antagonists, may be considered for GAS6+ patients to sensitize them to chemotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Masson K, Rönnstrand L . Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal 2009; 21: 1717–1726.

    Article  CAS  PubMed  Google Scholar 

  2. Correll PH, Paulson RF, Wei X . Molecular regulation of receptor tyrosine kinases in hematopoietic malignancies. Gene 2006; 374: 26–38.

    Article  CAS  PubMed  Google Scholar 

  3. Zheng R, Klang K, Gorin NC, Small D . Lack of KIT or FMS internal tandem duplications but co-expression with ligands in AML. Leuk Res 2004; 28: 121–126.

    Article  CAS  PubMed  Google Scholar 

  4. Malaise M, Steinbach D, Corbacioglu S . Clinical implications of c-Kit mutations in acute myelogenous leukemia. Curr Hematol Malig Rep 2009; 4: 77–82.

    Article  PubMed  Google Scholar 

  5. Sritana N, Auewarakul CU . KIT and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups. Exp Mol Pathol 2008; 85: 227–231.

    Article  CAS  PubMed  Google Scholar 

  6. Nanri T, Matsuno N, Kawakita T, Suzushima H, Kawano F, Mitsuya H et al. Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22). Leukemia 2005; 19: 1361–1366.

    Article  CAS  PubMed  Google Scholar 

  7. Paschka P, Marcucci G, Ruppert AS, Mrózek K, Chen H, Kittles RA et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B study. J Clin Oncol 2006; 24: 3904–3911.

    Article  CAS  PubMed  Google Scholar 

  8. Fröhling S, Scholl C, Gilliland DG, Levine RL . Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol 2005; 23: 6285–6295.

    Article  PubMed  Google Scholar 

  9. Hafizi S, Dahlbäck B . Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev 2006; 17: 295–304.

    Article  CAS  PubMed  Google Scholar 

  10. Verma A, Warner SL, Vankayalapati H, Bearss DJ, Sharma S . Targeting Axl and Mer kinases in cancer. Mol Cancer Ther 2011; 10: 1763–1773.

    Article  CAS  PubMed  Google Scholar 

  11. Brandão L, Migdall-Wilson J, Eisenman K, Graham DK . TAM receptors in leukemia: expression, signaling, and therapeutic implications. Crit Rev Oncog 2011; 16: 47–63.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Suárez RM, Chevot F, Cavagnino A, Saettel N, Radvanyi F, Piguel S et al. Inhibitors of the TAM subfamily of tyrosine kinases: synthesis and biological evaluation. Eur J Med Chem 2013; 61: 2–25.

    Article  PubMed  Google Scholar 

  13. Ye X, Li Y, Stawicki S, Couto S, Eastham-Anderson J, Kallop D et al. An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene 2010; 29: 5254–5264.

    Article  CAS  PubMed  Google Scholar 

  14. Lee-Sherick AB, Eisenman KM, Sather S, McGranahan A, Armistead PM, McGary CS et al. Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia. Oncogene 2013; 32: 5359–5368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Crosier PS, Hall LR, Vitas MR, Lewis PM, Crosier KE . Identification of a novel receptor tyrosine kinase expressed in acute myeloid leukemic blasts. Leuk Lymphoma 1995; 18: 443–449.

    Article  CAS  PubMed  Google Scholar 

  16. Rochlitz C, Lohri A, Bacchi M, Schmidt M, Nagel S, Fopp M et al. Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK). Leukemia 1999; 13: 1352–1358.

    Article  CAS  PubMed  Google Scholar 

  17. Manfioletti G, Brancolini C, Avanzi G, Schneider C . The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 1993; 13: 4976–4985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dirks W, Rome D, Ringel F, Jäger K, MacLeod RA, Drexler HG . Expression of the growth arrest-specific gene 6 (GAS6) in leukemia and lymphoma cell lines. Leuk Res 1999; 23: 643–651.

    Article  CAS  PubMed  Google Scholar 

  19. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994; 331: 896–903.

    Article  CAS  PubMed  Google Scholar 

  20. Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. N Engl J Med 1995; 332: 1671–1677.

    Article  CAS  PubMed  Google Scholar 

  21. Lee EJ, George SL, Caligiuri M, Szatrowski TP, Powell BL, Lemke S et al. Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of Cancer and Leukemia Group B study 9420. J Clin Oncol 1999; 17: 2831–2839.

    Article  CAS  PubMed  Google Scholar 

  22. Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K et al. Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B study 9720. J Clin Oncol 2008; 26: 4934–4939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Baer MR, George SL, Sanford BL, Mrózek K, Kolitz JE, Moore JO et al. Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B study 9720. Leukemia 2011; 25: 800–807.

    Article  CAS  PubMed  Google Scholar 

  24. Marcucci G, Moser B, Blum W, Stock W, Wetzler M, Kolitz JE et al. A phase III randomized trial of intensive induction and consolidation chemotherapy±oblimersen, a proapoptotic Bcl-2 antisense oligonucleotide in untreated acute myeloid leukemia patients &gt;60 years old [abstract]. J Clin Oncol 2007; 25: 360 (abstract 7012).

    Article  Google Scholar 

  25. Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL et al. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients under age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood 2010; 116: 1413–1421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mrózek K, Carroll AJ, Maharry K, Rao KW, Patil SR, Pettenati MJ et al. Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: the Cancer and Leukemia Group B experience. Int J Oncol 2008; 33: 239–244.

    PubMed  Google Scholar 

  27. Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B study. Cancer Res 2001; 61: 7233–7239.

    CAS  PubMed  Google Scholar 

  28. Whitman SP, Ruppert AS, Radmacher MD, Mrózek K, Paschka P, Langer C et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood 2008; 111: 1552–1559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Caligiuri MA, Strout MP, Schichman SA, Mrózek K, Arthur DC, Herzig GP et al. Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11. Cancer Res 1996; 56: 1418–1425.

    CAS  PubMed  Google Scholar 

  30. Whitman SP, Ruppert AS, Marcucci G, Mrózek K, Paschka P, Langer C et al. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study. Blood 2007; 109: 5164–5167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Becker H, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Margeson D et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 2010; 28: 596–604.

    Article  CAS  PubMed  Google Scholar 

  32. Marcucci G, Maharry K, Radmacher MD, Mrózek K, Vukosavljevic T, Paschka P et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B study. J Clin Oncol 2008; 26: 5078–5087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrózek K, Maharry K et al. Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2008; 26: 4595–4602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Metzeler KH, Maharry K, Radmacher MD, Mrózek K, Margeson D, Becker H et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2011; 29: 1373–1381.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Marcucci G, Maharry K, Wu Y-Z, Radmacher MD, Mrózek K, Margeson D et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2010; 28: 2348–2355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mendler JH, Maharry K, Radmacher MD, Mrózek K, Becker H, Metzeler KH et al. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures. J Clin Oncol 2012; 30: 3109–3118.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Metzeler KH, Becker H, Maharry K, Radmacher MD, Kohlschmidt J, Mrózek K et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood 2011; 118: 6920–6929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Marcucci G, Metzeler KH, Schwind S, Becker H, Maharry K, Mrózek K et al. Age related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol 2012; 30: 742–750.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Schwind S, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Holland KB et al. BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116: 5660–5669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Langer C, Marcucci G, Holland KB, Radmacher MD, Maharry K, Paschka P et al. Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2009; 27: 3198–3204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115: 453–474.

    Article  PubMed  Google Scholar 

  42. Ferrari F, Bortoluzzi S, Coppe A, Sirota A, Safran M, Shmoish M et al. Novel definition files for human GeneChips based on GeneAnnot. BMC Bioinformatics 2007; 8: 446.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003; 4: 249–264.

    Article  PubMed  Google Scholar 

  44. Klein JP, Moeschberger ML . Survival Analysis: Techniques for Censored and Truncated Data. Springer: New York, NY, USA, 2003.

    Google Scholar 

  45. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  46. Cox DR . Regression models and life-tables. J R Stat Soc Series B (Methodological) 1972; 34: 187–220.

    Article  Google Scholar 

  47. Jiang L, Yu G, Meng W, Wang Z, Meng F, Ma W . Overexpression of amyloid precursor protein in acute myeloid leukemia enhances extramedullary infiltration by MMP-2. Tumor Biol 2013; 34: 629–636.

    Article  CAS  Google Scholar 

  48. Cristóbal I, Blanco FJ, Garcia-Orti L, Marcotegui N, Vicente C, Rifon J et al. SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia. Blood 2010; 115: 615–625.

    Article  PubMed  Google Scholar 

  49. Alachkar H, Maharry K, Santhanam R, Neviani P, Volinia S, Kohlschmidt J et al. SPARC contributes to leukemia growth and aggressive disease in acute myeloid leukemia (AML). Blood 2012; 120, (abstract 773).

  50. Attar EC, Johnson JL, Amrein PC, Lozanski G, Wadleigh M, DeAngelo DJ et al. Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502. J Clin Oncol 2013; 31: 923–929.

    Article  CAS  PubMed  Google Scholar 

  51. Ahn JY, Seo K, Weinberg OK, Arber DA . The prognostic value of CXCR4 in acute myeloid leukemia. Appl Immunohistochem Mol Morphol 2013; 21: 79–84.

    CAS  PubMed  Google Scholar 

  52. Konoplev S, Rassidakis GZ, Estey E, Kantarjian H, Liakou CI, Huang X et al. Overexpression of CXCR4 predicts adverse overall and event-free survival in patients with unmutated FLT3 acute myeloid leukemia with normal karyotype. Cancer 2007; 109: 1152–1156.

    Article  CAS  PubMed  Google Scholar 

  53. Park IK, Mishra A, Chandler J, Whitman SP, Marcucci G, Caligiuri MA et al. Inhibition of the receptor tyrosine kinase Axl impedes activation of the FLT3 internal tandem duplication in human acute myeloid leukemia: implications for Axl as a potential therapeutic target. Blood 2013; 121: 2064–2073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ben-Batalla I, Schultze A, Wroblewski M, Erdmann R, Heuser M, Waizenegger JS et al. Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine cross-talk of leukemia cells with bone marrow stroma. Blood 2013; 122: 2443–2452.

    Article  CAS  PubMed  Google Scholar 

  55. Buehler M, Tse B, Leboucq A, Jacob F, Caduff R, Fink D et al. Meta-analysis of microarray data identifies GAS6 expression as an independent predictor of poor survival in ovarian cancer. Biomed Res Int 2013; 2013: 238284.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Hutterer M, Knyazev P, Abate A, Reschke M, Maier H, Stefanova N et al. Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme. Clin Cancer Res 2008; 14: 130–138.

    Article  CAS  PubMed  Google Scholar 

  57. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G . TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 2007; 131: 1124–1136.

    Article  CAS  PubMed  Google Scholar 

  58. Schmidt T, Ben-Batalla I, Schultze A, Loges S . Macrophage-tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands. Cell Mol Life Sci 2012; 69: 1391–1414.

    Article  CAS  PubMed  Google Scholar 

  59. Rankin EB, Fuh KC, Taylor TE, Krieg AJ, Musser M, Yuan J et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res 2010; 70: 7570–7579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hattermann K, Mentlein R . An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Ann Anat 2013; 195: 103–110.

    Article  CAS  PubMed  Google Scholar 

  61. Micallef IN, Stiff PJ, Stadtmauer EA, Bolwell BJ, Nademanee AP, Maziarz RT et al. Safety and efficacy of upfront plerixafor+G-CSF vs placebo+G-CSF for mobilization of CD34+ hematopoietic progenitor cells in patients ⩾60 and <60 years of age with non-Hodgkin's lymphoma or multiple myeloma. Am J Hematol 2013; 88: 1017–1023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM et al. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood 2012; 119: 3917–3924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Donna Bucci and the Alliance Leukemia Tissue Bank for sample processing and storage services, Lisa J Sterling and Christine Finks for data management and the OSU NCI-designated Comprehensive Cancer Center Microarray and Nucleic Acid shared resources for sample analyses. We also thank Dan Sargent for critical review of the manuscript. We also thank the physicians, nurses, clinical support staff and, most of all, patients for their invaluable contributions to these studies. This work was supported in part by the National Cancer Institute (Grants CA101140, CA114725, CA140158, CA31946, CA33601, CA16058, CA77658 and CA129657), the Coleman Leukemia Research Foundation, the Deutsche Krebshilfe—Dr Mildred Scheel Cancer Foundation (to HB), the Pelotonia Fellowship Program (to A-KE), and the Conquer Cancer Foundation (to JHM).

Author contributions

SPW, MAC, GM, CDB designed the study and analyzed the data. SPW, JK, K Maharry, K Mrózek, MAC, GM and CDB wrote the manuscript, and all authors agreed to the final version. JK, K Maharry, DN and SV performed statistical analyses. SPW, KHM, SW, HB, JM, A-KE, AJC and I-KP generated, compiled and interpreted the lab data. BLP, THC, MRB, JEK, RMS, MAC, GM, and CDB were involved directly or indirectly in the care of patients and/or sample procurement.

Author information

Author notes

  1. M A Caligiuri, G Marcucci and C D Bloomfield: These senior authors contributed equally to this work.

Authors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    S P Whitman, J Kohlschmidt, K Maharry, K Mrózek, D Nicolet, S Schwind, H Becker, K H Metzeler, J H Mendler, A-K Eisfeld, I-K Park, M A Caligiuri, G Marcucci & C D Bloomfield

  2. The Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    J Kohlschmidt, K Maharry & D Nicolet

  3. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, USA

    S Volinia

  4. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    A J Carroll

  5. The Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA

    B L Powell

  6. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA

    T H Carter

  7. Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    M R Baer

  8. North Shore University Hospital, Manhasset, NY, USA

    J E Kolitz

  9. Dana-Farber Cancer Institute, Boston, MA, USA

    R M Stone

Authors
  1. S P Whitman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Kohlschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Maharry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Volinia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Mrózek
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D Nicolet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Schwind
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K H Metzeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J H Mendler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A-K Eisfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A J Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. B L Powell
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. T H Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M R Baer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J E Kolitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. I-K Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. R M Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. M A Caligiuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. G Marcucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. C D Bloomfield
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C D Bloomfield.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whitman, S., Kohlschmidt, J., Maharry, K. et al. GAS6 expression identifies high-risk adult AML patients: potential implications for therapy. Leukemia 28, 1252–1258 (2014). https://doi.org/10.1038/leu.2013.371

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2013.371

Keywords

This article is cited by

Search

Advanced search

Quick links