Phenotypic heterogeneity in IGHV-mutated CLL patients has prognostic impact and identifies a subset with increased sensitivity to BTK and PI3Kδ inhibition

Leukemia

Volumn 29, Issue 3, 2015, Pages 744-747

  Pepper, C ^a   Buggins, A G S ^b   Jones, C H ^a   Walsby, E J ^a   Forconi, F ^c   Pratt, G ^d   Devereux, S ^b   Stevenson, F K ^c   Fegan, C ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA4 INTEGRIN; CHEMOKINE RECEPTOR CXCR4; IBRUTINIB; IDELALISIB; NATALIZUMAB; PLERIXAFOR; AGAMMAGLOBULINAEMIA TYROSINE KINASE; ANTINEOPLASTIC AGENT; CXCL12 PROTEIN, HUMAN; CXCR4 PROTEIN, HUMAN; HETEROCYCLIC COMPOUND; IMMUNOGLOBULIN HEAVY CHAIN; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PIK3CD PROTEIN, HUMAN; PROTEIN TYROSINE KINASE; PURINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINAZOLINONE DERIVATIVE; STROMAL CELL DERIVED FACTOR 1;

ANTIGEN EXPRESSION; CANCER DIAGNOSIS; CANCER GROWTH; CANCER PROGNOSIS; CELL MIGRATION; CELL PROTECTION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG EFFECT; DRUG SENSITIVITY; FLOW CYTOMETRY; GENE; GENE MUTATION; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; HUMAN; HUMAN CELL; IGHV GENE; IMMUNOGLOBULIN GENE; IN VITRO STUDY; LETTER; MAJOR CLINICAL STUDY; OVERALL SURVIVAL; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; SENSITIVITY ANALYSIS; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; GENE EXPRESSION REGULATION; GENETICS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; METABOLISM; MORTALITY; MUTATION; PATHOLOGY; PROGNOSIS; SIGNAL TRANSDUCTION; SURVIVAL;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; CHEMOKINE CXCL12; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC HETEROGENEITY; HETEROCYCLIC COMPOUNDS; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; INTEGRIN ALPHA4; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MUTATION; NATALIZUMAB; PROGNOSIS; PROTEIN-TYROSINE KINASES; PURINES; PYRAZOLES; PYRIMIDINES; QUINAZOLINONES; RECEPTORS, CXCR4; SIGNAL TRANSDUCTION; SURVIVAL ANALYSIS;

EID: 84924569820     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2014.308     Document Type: Letter

References (15)

1. Pepper C, Majid A, Lin TT, Hewamana S, Pratt G, Walewska R et al. Defining the prognosis of early stage chronic lymphocytic leukaemia patients. Br J Haematol 2012; 156: 499-507.
2. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 1848-1854.
3. Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840-1847.
4. Gladstone DE, Blackford A, Cho E, Swinnen L, Kasamon Y, Gocke CD et al. The importance of IGHV mutational status in del(11q) and del(17p) chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2012; 12: 132-137.
5. Burger JA. Chemokines and chemokine receptors in chronic lymphocytic leukemia (CLL): from understanding the basics towards therapeutic targeting. Semin Cancer Biol 2010; 20: 424-430.
6. O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014; 15: 48-58.
7. Majid A, Lin TT, Best G, Fishlock K, Hewamana S, Pratt G et al. CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leuk Res 2011; 35: 750-756.
8. Tobin G, Soderberg O, Thunberg U, Rosenquist R. V(H)3-21 gene usage in chronic lymphocytic leukemia - characterization of a new subgroup with distinct molecular features and poor survival. Leuk Lymphoma 2004; 45: 221-228.
9. Tobin G, Thunberg U, Johnson A, Thorn I, Soderberg O, Hultdin M et al. Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia. Blood 2002; 99: 2262-2264.
10. Bulian P, Shanafelt TD, Fegan C, Zucchetto A, Cro L, Nückel H et al. CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia. J Clin Oncol 2014; 32: 897-904.
11. Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 2012; 119: 1182-1189.
12. Walsby E, Buggins A, Devereux S, Jones C, Pratt G, Brennan P et al. Development and characterization of a physiologically relevant model of lymphocyte migration in chronic lymphocytic leukemia. Blood 2014; 123: 3607-3617.
13. Robak T, Robak P. BCR signaling in chronic lymphocytic leukemia and related inhibitors currently in clinical studies. Int Rev Immunol 2013; 32: 358-376.
14. Barrientos J, Rai K. Ibrutinib: a novel Bruton's tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia. Leuk Lymphoma 2013; 54 : 1817-1820.
15. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013; 369: 32-42.