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.

  • Article
  • Published:

LYMPHOMA

Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function

Leukemia volume 37, pages 2436–2447 (2023)Cite this article

Subjects

Abstract

As we show in this study, NAMPT, the key rate-limiting enzyme in the salvage pathway, one of the three known pathways involved in NAD synthesis, is selectively over-expressed in anaplastic T-cell lymphoma carrying oncogenic kinase NPM1::ALK (ALK + ALCL). NPM1::ALK induces expression of the NAMPT-encoding gene with STAT3 acting as transcriptional activator of the gene. Inhibition of NAMPT affects ALK + ALCL cells expression of numerous genes, many from the cell-signaling, metabolic, and apoptotic pathways. NAMPT inhibition also functionally impairs the key metabolic and signaling pathways, strikingly including enzymatic activity and, hence, oncogenic function of NPM1::ALK itself. Consequently, NAMPT inhibition induces cell death in vitro and suppresses ALK + ALCL tumor growth in vivo. These results indicate that NAMPT is a novel therapeutic target in ALK + ALCL and, possibly, other similar malignancies. Targeting metabolic pathways selectively activated by oncogenic kinases to which malignant cells become “addicted” may become a novel therapeutic approach to cancer, alternative or, more likely, complementary to direct inhibition of the kinase enzymatic domain. This potential therapy to simultaneously inhibit and metabolically “starve” oncogenic kinases may not only lead to higher response rates but also delay, or even prevent, development of drug resistance, frequently seen when kinase inhibitors are used as single agents.

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

Fig. 1: Expression of NAMPT by ALK + T cells and tissues.
Fig. 2: NPM1::ALK-dependence of NAMPT expression.
Fig. 3: STAT3-dependence of NAMPT expression.
Fig. 4: NAMPT-dependence of ALK + T cells.
Fig. 5: Inhibition of NAMPT induces functional changes in ALK + ALCL cells.
Fig. 6: NAMPT inhibition induces apoptosis of ALK + T cells.
Fig. 7: Inhibition of NAMPT suppresses growth of ALK + ALCL cells in vivo.
Fig. 8: Schematic diagram of the mechanistic links between NPM1::ALK and NAMPT.

Similar content being viewed by others

Data availability

Data sets used or generated in this study can be accessed through the GEO portal (GSE8685 and GSE17889). For additional information, please contact the corresponding author at Mariusz.Wasik@fccc.edu.

References

  1. Yao S, Cheng M, Zhang Q, Wasik M, Kelsh R, Winkler C. Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish. PLoS One. 2013;8:e63757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Boi M, Zucca E, Inghirami G, Bertoni F. Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas. Br J Haematol. 2015;168:771–83.

    Article  CAS  PubMed  Google Scholar 

  3. Pall G. The next-generation ALK inhibitors. Curr Opin Oncol. 2015;27:118–24.

    Article  CAS  PubMed  Google Scholar 

  4. Werner MT, Zhao C, Zhang Q, Wasik MA. Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target. Blood. 2017;129:823–31.

    Article  CAS  PubMed  Google Scholar 

  5. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263:1281–4.

    Article  CAS  PubMed  Google Scholar 

  6. Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S. Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene. 1994;9:1567–74.

    CAS  PubMed  Google Scholar 

  7. Bischof D, Pulford K, Mason DY, Morris SW. Role of the nucleophosmin (NPM) portion of the non-Hodgkin’s lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. Mol Cell Biol. 1997;17:2312–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chiarle R, Gong JZ, Guasparri I, Pesci A, Cai J, Liu J, et al. NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors. Blood. 2003;101:1919–27.

    Article  CAS  PubMed  Google Scholar 

  9. Fujimoto J, Shiota M, Iwahara T, Seki N, Satoh H, Mori S, et al. Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5). Proc Natl Acad Sci USA. 1996;93:4181–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kuefer MU, Look AT, Pulford K, Behm FG, Pattengale PK, Mason DY, et al. Retrovirus-mediated gene transfer of NPM-ALK causes lymphoid malignancy in mice. Blood. 1997;90:2901–10.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang Q, Wei F, Wang HY, Liu X, Roy D, Xiong QB, et al. The potent oncogene NPM-ALK mediates malignant transformation of normal human CD4(+) T lymphocytes. Am J Pathol. 2013;183:1971–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Marzec M, Halasa K, Liu X, Wang HY, Cheng M, Baldwin D, et al. Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming. J Immunol. 2013;191:6200–7.

    Article  CAS  PubMed  Google Scholar 

  13. Chiarle R, Simmons WJ, Cai H, Dhall G, Zamo A, Raz R, et al. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat Med. 2005;11:623–9.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Q, Raghunath PN, Xue L, Majewski M, Carpentieri DF, Odum N, et al. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. J Immunol. 2002;168:466–74.

    Article  CAS  PubMed  Google Scholar 

  15. Kasprzycka M, Marzec M, Liu X, Zhang Q, Wasik MA. Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3. Proc Natl Acad Sci USA. 2006;103:9964–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X, Paessler M, et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci USA. 2008;105:20852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang Q, Wang H, Kantekure K, Paterson JC, Liu X, Schaffer A, et al. Oncogenic tyrosine kinase NPM-ALK induces expression of the growth-promoting receptor ICOS. Blood. 2011;118:3062–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Martinengo C, Poggio T, Menotti M, Scalzo MS, Mastini C, Ambrogio C, et al. ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis. Cancer Res. 2014;74:6094–106.

    Article  CAS  PubMed  Google Scholar 

  19. Marzec M, Liu X, Wong W, Yang Y, Pasha T, Kantekure K, et al. Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA. Oncogene. 2011;30:1372–8.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Q, Wang HY, Liu X, Wasik MA. STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression. Nat Med. 2007;13:1341–8.

    Article  CAS  PubMed  Google Scholar 

  21. Gallí M, Van Gool F, Rongvaux A, Andris F, Leo O. The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer. Cancer Res. 2010;70:8–11.

    Article  PubMed  Google Scholar 

  22. Shackelford RE, Mayhall K, Maxwell NM, Kandil E, Coppola D. Nicotinamide phosphoribosyltransferase in malignancy: a review. Genes Cancer. 2013;4:447–56.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Heske CM. Beyond energy metabolism: exploiting the additional roles of NAMPT for cancer therapy. Front Oncol. 2019;9:1514.

    Article  PubMed  Google Scholar 

  24. Zhang Q, Wang HY, Nayak A, Nunez-Cruz S, Slupianek A, Liu X, et al. Induction of transcriptional inhibitor HES1 and the related repression of tumor-suppressor TXNIP are important components of cell-transformation program imposed by oncogenic kinase NPM-ALK. Am J Pathol. 2022;192:1186–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pawlicki JM, Cookmeyer DL, Maseda D, Everett JK, Wei F, Kong H, et al. NPM-ALK-induced reprogramming of mature TCR-stimulated T cells results in dedifferentiation and malignant transformation. Cancer Res. 2021;81:3241–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang JP, Song Z, Wang HB, Lang L, Yang YZ, Xiao W, et al. A novel model of controlling PD-L1 expression in ALK. Blood. 2019;134:171–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bellet MM, Orozco-Solis R, Sahar S, Eckel-Mahan K, Sassone-Corsi P. The time of metabolism: NAD+, SIRT1, and the circadian clock. Cold Spring Harb Symp Quant Biol. 2011;76:31–8.

    Article  CAS  PubMed  Google Scholar 

  28. Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Lüscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci USA. 2012;109:E187–96.

    Article  CAS  PubMed  Google Scholar 

  29. Nowell MA, Richards PJ, Fielding CA, Ognjanovic S, Topley N, Williams AS, et al. Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 2006;54:2084–95.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Q, Wang HY, Liu X, Bhutani G, Kantekure K, Wasik M. IL-2R common gamma-chain is epigenetically silenced by nucleophosphin-anaplastic lymphoma kinase (NPM-ALK) and acts as a tumor suppressor by targeting NPM-ALK. Proc Natl Acad Sci USA. 2011b;108:11977–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Holen K, Saltz LB, Hollywood E, Burk K, Hanauske AR. The pharmacokinetics, toxicities, and biologic effects of FK866, a nicotinamide adenine dinucleotide biosynthesis inhibitor. Invest N. Drugs. 2008;26:45–51.

    Article  CAS  Google Scholar 

  32. Zhang Q, Wang HY, Woetmann A, Raghunath PN, Odum N, Wasik MA. STAT3 induces transcription of the DNA methyltransferase 1 gene (DNMT1) in malignant T lymphocytes. Blood. 2006;108:1058–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang Q, Raghunath PN, Vonderheid E, Odum N, Wasik MA. Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter. Am J Pathol. 2000;157:1137–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang Q, Wang HY, Marzec M, Raghunath PN, Nagasawa T, Wasik MA. STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. Proc Natl Acad Sci USA. 2005;102:6948–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wei Y, Xiang H, Zhang W. Review of various NAMPT inhibitors for the treatment of cancer. Front Pharm. 2022;13:970553.

    Article  CAS  Google Scholar 

  36. Issaq SH, Heske CM. Targeting metabolic dependencies in pediatric cancer. Curr Opin Pediatr. 2020;32:26–34.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Gasparrini M, Audrito V. NAMPT: a critical driver and therapeutic target for cancer. Int J Biochem Cell Biol. 2022;145:106189.

    Article  CAS  PubMed  Google Scholar 

  38. Nagel S, Pommerenke C, MacLeod RAF, Meyer C, Kaufmann M, Drexler HG. The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL). Oncotarget. 2020;11:3208–26.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Marzec M, Kasprzycka M, Liu X, El-Salem M, Halasa K, Raghunath PN, et al. Oncogenic tyrosine kinase NPM/ALK induces activation of the rapamycin-sensitive mTOR signaling pathway. Oncogene. 2007;26:5606–14.

    Article  CAS  PubMed  Google Scholar 

  40. Crescenzo R, Abate F, Lasorsa E, Tabbo F, Gaudiano M, et al. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 2015;27:516–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lu L, Ghose AK, Quail MR, Albom MS, Durkin JT, Holskin BP, et al. ALK mutants in the kinase domain exhibit altered kinase activity and differential sensitivity to small molecule ALK inhibitors. Biochemistry. 2009;48:3600–9.

    Article  CAS  PubMed  Google Scholar 

  42. Marzec M, Kasprzycka M, Ptasznik A, Wlodarski P, Zhang Q, Odum N, et al. Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3. Lab Investig. 2005;85:1544–54.

    Article  CAS  PubMed  Google Scholar 

  43. Gambacorti-Passerini C, Messa C, Pogliani EM. Crizotinib in anaplastic large-cell lymphoma. N Engl J Med. 2011;364:775–6.

    Article  PubMed  Google Scholar 

  44. Gambacorti Passerini C, Farina F, Stasia A, Redaelli S, Ceccon M, Mologni L, et al. Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J Natl Cancer Inst. 2014;106:djt378.

    Article  PubMed  Google Scholar 

  45. Mossé YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14:472–80.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Pearson ADJ, Barry E, Mossé YP, Ligas F, Bird N, de Rojas T, et al. Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration. Eur J Cancer. 2021;157:198–213.

    Article  CAS  PubMed  Google Scholar 

  47. Camidge DR, Doebele RC. Treating ALK-positive lung cancer–early successes and future challenges. Nat Rev Clin Oncol. 2012;9:268–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kwak EL, Clark JW, Shaw AT. Targeted inhibition in tumors with ALK dependency. Lung Cancer. 2013;4:1–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.

    Article  CAS  PubMed  Google Scholar 

  50. Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363:1734–9.

    Article  CAS  PubMed  Google Scholar 

  51. Wang Y, He J, Xu M, Xue Q, Zhu C, Liu J, et al. Holistic view of ALK TKI resistance in ALK-positive anaplastic large cell lymphoma. Front Oncol. 2022;12:815654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gehrke I, Bouchard ED, Beiggi S, Poeppl AG, Johnston JB, Gibson SB, et al. On-target effect of FK866, a nicotinamide phosphoribosyl transferase inhibitor, by apoptosis-mediated death in chronic lymphocytic leukemia cells. Clin Cancer Res. 2014;20:4861–72.

    Article  CAS  PubMed  Google Scholar 

  53. Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, et al. The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies. Blood. 2009;113:3276–86.

    Article  CAS  PubMed  Google Scholar 

  54. Nahimana A, Aubry D, Breton CS, Majjigapu SR, Sordat B, Vogel P, et al. The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody. Leuk Lymphoma. 2014;55:2141–50.

    Article  CAS  PubMed  Google Scholar 

  55. Gibson AE, Yeung C, Issaq SH, Collins VJ, Gouzoulis M, Zhang Y, et al. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma. Oncogenesis. 2020;9:80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sampath D, Zabka TS, Misner DL, O’Brien T, Dragovich PS. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer. Pharm Ther. 2015;151:16–31.

    Article  CAS  Google Scholar 

  57. Tateishi K, Wakimoto H, Iafrate AJ, Tanaka S, Loebel F, Lelic N, et al. Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion. Cancer Cell. 2015;28:773–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126:17–25.

    Article  CAS  PubMed  Google Scholar 

  59. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017;130:2709–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. CircaDB: http://circadb.hogeneschlab.org.

Download references

Funding

Supported in part by grants from National Cancer Institute R01CA96856 and R01CA228457 and funds from the Abramson Cancer Center Translational Center of Excellence in Lymphoma, Daniel B. Allanoff Foundation, and Fox Chase Cancer Center Institute for Cancer Research.

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Qian Zhang, Hong Y. Wang, Selene Nunez-Cruz, Xiaobin Liu, Seble Chekol, Amy Ziober, Reza Nejati, Michael Feldman & Mariusz A. Wasik

  2. Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Johnvesly Basappa, Cosimo Lobello, Shengchun Wang & Mariusz A. Wasik

  3. Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA

    Lili Guo & Ian A. Blair

  4. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Alex Shestov & Jerry D. Glickson

  5. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael Feldman, Chi Van Dang & Mariusz A. Wasik

  6. Department of Pathology, University of Cambridge, Cambridge, UK

    Suzanne D. Turner

  7. The Wistar Institute, Philadelphia, PA, USA

    Chi Van Dang

Authors
  1. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johnvesly Basappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selene Nunez-Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cosimo Lobello
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shengchun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaobin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seble Chekol
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lili Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Amy Ziober
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Reza Nejati
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alex Shestov
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jerry D. Glickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Suzanne D. Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ian A. Blair
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Chi Van Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Mariusz A. Wasik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QZ, JB, S N-C, CVD, and MAW designed research; QZ, JB, HYW, S N-C, SW, XL, LG, AZ, and CL performed research; JS, MF, and IB contributed new reagents/analytic tools; QZ, JB, HYW, S N-C, S C, RN, AS, JG, SDT, and MAW analyzed data; MAW wrote the paper.

Corresponding author

Correspondence to Mariusz A. Wasik.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Basappa, J., Wang, H.Y. et al. Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function. Leukemia 37, 2436–2447 (2023). https://doi.org/10.1038/s41375-023-02038-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-023-02038-0

Search

Advanced search

Quick links