CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.
CXCR4 gain of function
EBV-related lymphomas
HPV-induced carcinomas
WHIM syndrome
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
revised:
31
01
2024
received:
23
11
2023
accepted:
20
02
2024
medline:
6
3
2024
pubmed:
6
3
2024
entrez:
5
3
2024
Statut:
aheadofprint
Résumé
Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by the gain of function of the CXCR4 chemokine receptor. We present the prevalence of cancer in WHIMS patients based on data from the French Severe Chronic Neutropenia Registry and an exhaustive literature review. The median follow-up of the 14 WHIMS 'patients was 28.5 years. A central review and viral evaluation of pathological samples were organized, and we conducted a thorough literature review to identify all reports of WHIMS cases. Six French patients were diagnosed with cancer at a median age of 37.6 years. The 40-year risk of malignancy was 39% (95% confidence interval [CI]: 6%-74%). We observed two human papillomavirus (HPV)-induced vulvar carcinomas, three lymphomas (two Epstein-Barr virus [EBV]-related) and one basal cell carcinoma. Among the 155 WHIMS cases from the literature, 22 cancers were reported in 16 patients, with an overall cancer 40-year risk of 23% (95% CI: 13%-39%). Malignancies included EBV-associated lymphoproliferative disorders and HPV-positive genital and anal cancers as in the French cohort. Worldwide, nine cases of malignancy were associated with HPV and four with EBV. Immunocompromised WHIMS patients appear to be particularly susceptible to developing early malignancy, mainly HPV-induced carcinomas, followed by EBV-related lymphomas.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Krill CE, Smith HD, Mauer AM. Chronic idiopathic granulocytopenia. N Engl J Med. 1964;270(19):973-979.
Zuelzer WW. ‘Myelokathexis’-a new form of chronic granulocytopenia. Report of a case. N Engl J Med. 1964;270:699-704.
Badolato R, Donadieu J, WHIM Research Group. How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. Blood. 2017;130(23):2491-2498.
Beaussant Cohen S, Fenneteau O, Plouvier E, Rohrlich PS, Daltroff G, Plantier I, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French severe chronic neutropenia registry. Orphanet J Rare Dis. 2012;7(1):71.
Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet. 2003;34(1):70-74.
Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, et al. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood. 2005;105(6):2449-2457.
Hernández-López C, Varas A, Sacedón R, Jiménez E, Muñoz JJ, Zapata AG, et al. Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development. Blood. 2002;99(2):546-554.
Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998;393(6685):595-599.
Freitas C, Wittner M, Nguyen J, Rondeau V, Biajoux V, Aknin ML, et al. Lymphoid differentiation of haematopoietic stem cells requires efficient Cxcr4 desensitization. J Exp Med. 2017;214(7):2023-2040.
Ganju RK, Brubaker SA, Meyer J, Dutt P, Yang Y, Qin S, et al. The α-chemokine, stromal cell-derived factor-1α, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways*. J Biol Chem. 1998;273(36):23169-23175.
McDermott DH, Murphy PM. WHIM syndrome: Immunopathogenesis, treatment and cure strategies. Immunol Rev. 2019;287(1):91-102.
Dale DC, Bolyard AA, Kelley ML, Westrup EC, Makaryan V, Aprikyan A, et al. The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM Syndrome. Blood. 2011;118(18):4963-4966.
McDermott DH, Pastrana DV, Calvo KR, Pittaluga S, Velez D, Cho E, et al. Plerixafor for the treatment of WHIM syndrome. N Engl J Med. 2019;380(2):163-170.
McDermott DH, Liu Q, Velez D, Lopez L, Anaya-O'Brien S, Ulrick J, et al. A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood. 2014;123(15):2308-2316.
McDermott DH, Liu Q, Ulrick J, Kwatemaa N, Anaya-O'Brien S, Penzak SR, et al. The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. Blood. 2011;118(18):4957-4962.
McDermott DH, Velez D, Cho E, Cowen EW, DiGiovanna JJ, Pastrana DV, et al. A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome. J Clin Invest. 2023;133(19):e164918.
Dale DC, Firkin F, Bolyard AA, Kelley M, Makaryan V, Gorelick KJ, et al. Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome. Blood. 2020;136(26):2994-3003.
Xu L, Padalko E, Oštrbenk A, Poljak M, Arbyn M. Clinical evaluation of INNO-LiPA HPV genotyping EXTRA II assay using the VALGENT framework. Int J Mol Sci. 2018;19(9):2704.
Halec G, Alemany L, Quiros B, Clavero O, Höfler D, Alejo M, et al. Biological relevance of human papillomaviruses in vulvar cancer. Mod Pathol off J U S Can Acad Pathol Inc. 2017;30(4):549-562.
Erdős M. Molekuláris genetikai vizsgálatok primer immundefektusokban. Orv Hetil. 2018;159(49):2095-2112.
Ohtake M, Kobayashi M, Watanabe N, Nagai Y, Kato S, Ikuo K. A clinical report of the first case of myelokathexis in Japan. J Jpn Pediatr Soc. 1988;92:160-165.
Colonna M, Mitton N, Bossard N, Belot A, Grosclaude P. The French network of cancer registries (FRANCIM). Total and partial cancer prevalence in the adult French population in 2008. BMC Cancer. 2015;15(1):153.
Colonna M, Boussari O, Cowppli-Bony A, Delafosse P, Romain G, Grosclaude P, et al. Time trends and short term projections of cancer prevalence in France. Cancer Epidemiol. 2018;56:97-105.
Ward EM, Sherman RL, Henley SJ, Jemal A, Siegel DA, Feuer EJ, et al. Annual report to the nation on the status of cancer, featuring cancer in men and women age 20-49 years. J Natl Cancer Inst. 2019;111(12):1279-1297.
Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM, Howlader N, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2018;124(13):2785-2800.
Pastrana DV, Peretti A, Welch NL, Borgogna C, Olivero C, Badolato R, et al. Metagenomic Discovery of 83 New Human Papillomavirus Types in Patients with Immunodeficiency. mSphere. 2018;3(6):e00645-e00718.
Dotta L, Notarangelo LD, Moratto D, Kumar R, Porta F, Soresina A, et al. Long-term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related malignancies. J Allergy Clin Immunol Pract. 2019;7(5):1568-1577.
Gulino AV, Moratto D, Sozzani S, Cavadini P, Otero K, Tassone L, et al. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Blood. 2004;104(2):444-452.
Alouche N, Bonaud A, Rondeau V, Hussein-Agha R, Nguyen J, Bisio V, et al. Haematological disorder-associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response. Blood. 2021;137(22):3050-3063.
McDermott DH, Gao JL, Liu Q, Siwicki M, Martens C, Jacobs P, et al. Chromothriptic cure of WHIM syndrome. Cell. 2015;160(4):686-699.
Tassone L, Moratto D, Vermi W, De Francesco M, Notarangelo LD, Porta F, et al. Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients. Blood. 2010;116(23):4870-4873.
Gallego C, Vétillard M, Calmette J, Roriz M, Marin-Esteban V, Evrard M, et al. CXCR4 signaling controls dendritic cell location and activation at steady state and in inflammation. Blood. 2021;137(20):2770-2784.
Chow KYC, Brotin É, Ben Khalifa Y, Carthagena L, Teissier S, Danckaert A, et al. A pivotal role for CXCL12 signaling in HPV-mediated transformation of keratinocytes: clues to understanding HPV-pathogenesis in WHIM syndrome. Cell Host Microbe. 2010;8(6):523-533.
Meuris F, Carthagena L, Jaracz-Ros A, Gaudin F, Cutolo P, Deback C, et al. The CXCL12/CXCR4 signaling pathway: a new susceptibility factor in human papillomavirus pathogenesis. PLoS Pathog. 2016;12(12):e1006039.
Allen CDC, Ansel KM, Low C, Lesley R, Tamamura H, Fujii N, et al. Germinal centre dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol. 2004;5(9):943-952.
Beck TC, Gomes AC, Cyster JG, Pereira JP. CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. J Exp Med. 2014;211(13):2567-2581.
Nie Y, Waite J, Brewer F, Sunshine MJ, Littman DR, Zou YR. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J Exp Med. 2004;200(9):1145-1156.
Chatterjee S, Azad BB, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res. 2014;124:31-82.
Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene. 2016;35(7):816-826.
Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410(6824):50-56.
Handisurya A, Schellenbacher C, Reininger B, Koszik F, Vyhnanek P, Heitger A, et al. A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome. Vaccine. 2010;28(30):4837-4841.
Tassone L, Notarangelo LD, Bonomi V, Savoldi G, Sensi A, Soresina A, et al. Clinical and genetic diagnosis of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome in 10 patients. J Allergy Clin Immunol. 2009;123(5):1170-1173.e3.
Cheng L, Wang Y, Du J. Human papillomavirus vaccines: an updated review. Vaccine. 2020;8(3):391.
Bednarczyk RA, Brewer NT, Gilkey MB, Zorn S, Perkins RB, Oliver K, et al. Human papillomavirus vaccination at the first opportunity: an overview. Hum Vaccin Immunother. 2023;19(1):2213603.
Saslow D, Andrews KS, Manassaram-Baptiste D, Smith RA, Fontham ETH. American Cancer Society guideline development group. Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation. CA Cancer J Clin. 2020;70(4):274-280.
Marin-Esteban V, Molet L, Lagana M, Ciocan D, Dominguez-Lafage C, Alouche N, et al. Impact of a CXCR4 antagonist on the long-term remission of HPV5-associated perianal squamous cell carcinoma. N Engl J Med. 2024;In press.
Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res off J Am Assoc Cancer Res. 2011;17(8):2074-2080.
Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020;26(6):878-885.
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 leukaemia. Blood. 2012;119(17):3917-3924.