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Portal Hypertension and Progressive Lymphoproliferation

  • Svetlana O. Sharapova
Chapter

Abstract

Activated phosphoinositide 3-kinase δ syndrome type 1 (APSD type 1) is caused by gain-of-function mutations in the gene encoding p110δ subunit of PI3K

Constitutive activation of the PI3K/Akt/mTOR pathway and mTOR pathway is the primary cause of abnormal lymphoproliferation in APDS

Rapamycin has been shown to improve lymphoproliferative symptoms in APDS

Leniolisib is a small molecule inhibitor of p110δ and improves lymphoproliferative symptoms and abnormal pattern of T cell population

Keywords

Activated phosphoinositide 3-kinase δ syndrome Leniolisib Rapamycin Lymphoproliferation 

References

  1. 1.
    Dufour C, Miano M, Fioredda F. Old and new faces of neutropenia in children. Haematologica. 2016;101(7):789–91.CrossRefGoogle Scholar
  2. 2.
    Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, Goodlad JR, Farmer G, Steele CL, Leahy TR, Doffinger R, Baxendale H, Bernatoniene J, Edgar JD, Longhurst HJ, Ehl S, Speckmann C, Grimbacher B, Sediva A, Milota T, Faust SN, Williams AP, Hayman G, Kucuk ZY, Hague R, French P, Brooker R, Forsyth P, Herriot R, Cancrini C, Palma P, Ariganello P, Conlon N, Feighery C, Gavin PJ, Jones A, Imai K, Ibrahim MA, Markelj G, Abinun M, Rieux-Laucat F, Latour S, Pellier I, Fischer A, Touzot F, Casanova JL, Durandy A, Burns SO, Savic S, Kumararatne DS, Moshous D, Kracker S, Vanhaesebroeck B, Okkenhaug K, Picard C, Nejentsev S, Condliffe AM, Cant AJ. Clinical spectrum and features of activated phosphoinositide 3-kinase delta syndrome: a large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597–606.e4.CrossRefGoogle Scholar
  3. 3.
    Wentink M, Dalm V, Lankester AC, van Schouwenburg PA, Scholvinck L, Kalina T, Zachova R, Sediva A, Lambeck A, Pico-Knijnenburg I, van Dongen JJ, Pac M, Bernatowska E, van Hagen M, Driessen G, van der Burg M. Genetic defects in PI3Kdelta affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections. Clin Immunol. 2017;176:77–86.CrossRefGoogle Scholar
  4. 4.
    Heurtier L, Lamrini H, Chentout L, Deau MC, Bouafia A, Rosain J, Plaza JM, Parisot M, Dumont B, Turpin D, Merlin E, Moshous D, Aladjidi N, Neven B, Picard C, Cavazzana M, Fischer A, Durandy A, Stephan JL, Kracker S. Mutations in the adaptor-binding domain and associated linker region of p110delta cause Activated PI3K-delta Syndrome 1 (APDS1). Haematologica. 2017;102(7):e278–e81.CrossRefGoogle Scholar
  5. 5.
    Rao VK, Webster S, Dalm V, Sediva A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective “activated PI3Kdelta syndrome”-targeted therapy with the PI3Kdelta inhibitor leniolisib. Blood. 2017;130(21):2307–16.CrossRefGoogle Scholar
  6. 6.
    Elkaim E, Neven B, Bruneau J, Mitsui-Sekinaka K, Stanislas A, Heurtier L, Lucas CL, Matthews H, Deau MC, Sharapova S, Curtis J, Reichenbach J, Glastre C, Parry DA, Arumugakani G, McDermott E, Kilic SS, Yamashita M, Moshous D, Lamrini H, Otremba B, Gennery A, Coulter T, Quinti I, Stephan JL, Lougaris V, Brodszki N, Barlogis V, Asano T, Galicier L, Boutboul D, Nonoyama S, Cant A, Imai K, Picard C, Nejentsev S, Molina TJ, Lenardo M, Savic S, Cavazzana M, Fischer A, Durandy A, Kracker S. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase delta syndrome 2: a cohort study. J Allergy Clin Immunol. 2016;138(1):210–8.e9.CrossRefGoogle Scholar
  7. 7.
    Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88–97.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Svetlana O. Sharapova
    • 1
  1. 1.Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Research Department, Immunology LaboratoryMinsk RegionBelarus

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