Page 191 - Haematologica - Vol. 105 n. 6 - June 2020

PIKfyve inhibition in multiple myeloma
2007;109(3):1156-1164.
7. Wada Y, Cardinale I, Khatcherian A, et al.
Apilimod inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltra- tion in psoriasis. PLoS One. 2012;7(4): e35069.
8. Krausz S, Boumans MJH, Gerlag DM, et al. A phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesy- late, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(6):1750- 1755.
9. Sands BE, Jacobson EW, Sylwestrowicz T, et al. Randomized, double-blind, placebo- controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn’s disease. Inflamm Bowel Dis. 2010;16(7):1209-1218.
10. Burakoff R, Barish CF, Riff D, et al. A phase 1/2A trial of STA5326, an oral interleukin- 12/23 inhibitor, in patients with active moderate to severe Crohn’s disease. Inflamm Bowel Dis. 2006;12(7):558-565.
11. Cai X, Xu Y, Cheung AK, et al. PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in toll-like receptor signaling. Chem Biol. 2013;20(7):912-921.
12. Gayle S, Landrette S, Beeharry N, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B- cell non-Hodgkin lymphoma. Blood. 2017;129(13):1768-1778.
13. Jefferies HBJ, Cooke FT, Jat P, et al. A selec- tive PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding. EMBO Rep. 2008;9(2):164-170.
14. Hayakawa N, Noguchi M, Takeshita S, et al. Structure–activity relationship study, target identification, and pharmacological charac- terization of a small molecular IL-12 /23. Bioorg Med Chem. 2014;22(11):3021-3029.
15. Terajima M, Kaneko-Kobayashi Y, Nakamura N, et al. Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor. Eur J Pharmacol. 2016;780:93-105.
16. de Lartigue J, Polson H, Feldman M, et al. PIKfyve regulation of endosome-linked pathways. Traffic. 2009;10(7):883-893.
17. Meurice N, Petit J, De Campos C, et al. “Direct to drug” screening as a route to individualized therapy in multiple myelo- ma. Blood. 2017;130(Suppl 1):3080.
18. Seckinger A, Delgado JA, Moser S, et al. Target expression, generation, preclinical
activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31(3):396-410.
19. Kalari KR, Nair AA, Bhavsar JD, et al. MAP- RSeq: Mayo analysis pipeline for RNA sequencing. BMC Bioinformatics. 2014;15: 224-15234.
20. Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21.
21. Wang L, Wang S, Li W. RSeQC: quality control of RNA-seq experiments. Bioinformatics. 2012;28(16):2184-2185.
22. Liao Y, Smyth GK, Shi W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic fea- tures. Bioinformatics. 2014;30(7):923-930.
23. Kuleshov M V, Jones MR, Rouillard AD, et al. Enrichr : a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:90-97.
24. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expres- sion and hybridization array data reposito- ry. Nucleic Acids Res. 2002;30(1):207-210.
25. Wuilleme S, Robillard N, Lodé L, et al. Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia. 2005;19(2):275-278.
26. Choy CH, Saffi G, Gray MA, et al. Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence. J Cell Sci. 2018;131(10).
27. Aggarwal R, Ghobrial IM, Roodman GD. Chemokines in multiple myeloma. Exp Hematol. 2006;34(10):1289-1295.
28. Masih-Khan E, Trudel S, Heise C, et al. MIP-1alpha (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in mul- tiple myeloma. Blood. 2006;108(10):3465- 3471.
29. Napolitano G, Ballabio A. TFEB at a glance. J Cell Sci. 2016;129(13):2475-2481.
30. Settembre C, Ballabio A. TFEB regulates autophagy: an integrated coordination of cellular degradation and recycling process- es. Autophagy. 2011;7(11):1379-1381.
31. Krishna S, Palm W, Lee Y, et al. PIKfyve reg- ulates vacuole maturation and nutrient recovery following engulfment. Dev Cell. 2016;38(5):536-547.
32. Aits S, Jaattela M. Lysosomal cell death at a glance. J Cell Sci. 2013;126(9):1905-1912.
33. Kara NZ, Toker L, Agam G, et al. Trehalose induced antidepressant-like effects and
autophagy enhancement in mice.
Psychopharmacology. 2013;229(2):367-375. 34. Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edi-
tion). Autophagy. 2016;12(1):1-222.
35. Sonneveld P. Management of multiple myeloma in the relapsed/refractory patient. Hematol Am Soc Hematol Educ Progr.
2017;2017(1):508-517.
36. Manier S, Salem KZ, Park J, et al. Genomic
complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol. 2016;13:100-113.
37. Laubach J, Garderet L, Mahindra A, et al. Management of relapsed multiple myelo- ma: recommendations of the International Myeloma Working Group. Leukemia. 2016;30(5):1005-1017.
38. Gayle S, Landrette S, Beeharry N, et al. B- cell non-Hodgkin lymphoma: selective vul- nerability to PIKFYVE inhibition. Autophagy. 2017;13(6):1082-1083.
39. Ikonomov OC, Sbrissa D, Shisheva A. YM201636, an inhibitor of retroviral bud- ding and PIKfyve-catalyzed PtdIns (3,5)P2 synthesis, halts glucose entry by insulin in adipocytes. Biochem Biophys Res Commun. 2009;382(3):566-570.
40. Wang W, Gao Q, Yang M, et al. Up-regula- tion of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutri- ent starvation. Proc Natl Acad Sci U S A. 2015;112(11):1373-1381.
41. Pengo N, Scolari M, Oliva L, et al. Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol. 2013;14(3):298-305.
42. Settembre C, Polito VA, Garcia M, et al. TFEB links autophagy to lysosomal biogen- esis. Science. 2011;332(6036):1429-1433.
43. Milan E, Fabbri M, Cenci S. Autophagy in plasma cell ontogeny and malignancy. J Clin Immunol. 2016;36(Suppl 1):S18-S24.
44. Milan E, Perini T, Resnati M, et al. A plastic SQSTM1/p62-dependent autophagic reserve maintains proteostasis and deter- mines proteasome inhibitor susceptibility in multiple myeloma cells. Autophagy. 2015;11(7):1161-1178.
45. Harb WA, Diefenbach CS, Lakhani N, et al. Phase 1 clinical safety, pharmacokinetics (PK), and activity of apilimod dimesylate (LAM-002A), a first-in-class inhibitor of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), in patients with relapsed or refractory B-cell malignancies. Blood. 2017;130(Suppl 1):4119.
haematologica | 2020; 105(6)
1649