Genetic lesions in chronic lymphocytic leukemia: what’s ready for prime time use?

Chronic lymphocytic leukemia (CLL) is a frequent CD5+ B-cell neoplasia that involves peripheral blood, bone marrow, lymph nodes and other lymphoid tissues. The median age of patients at diagnosis of CLL is around 70 years old and the prognosis is extremely variable. In spite of some advances in its

[1]  A Benner,et al.  Genomic aberrations and survival in chronic lymphocytic leukemia. , 2000, The New England journal of medicine.

[2]  Hartmut Döhner,et al.  Molecular diagnostics in chronic lymphocytic leukemia – Pathogenetic and clinical implications , 2008, Leukemia & lymphoma.

[3]  T J Hamblin,et al.  Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. , 1999, Blood.

[4]  H. Kantarjian,et al.  Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia , 2009, Cancer.

[5]  M. Lowery-Nordberg,et al.  Atypical 11q deletions identified by array CGH may be missed by FISH panels for prognostic markers in chronic lymphocytic leukemia , 2009, Leukemia.

[6]  T Hamblin,et al.  Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial , 2007, The Lancet.

[7]  Terry J. Hamblin,et al.  Unmutated Ig VH Genes Are Associated With a More Aggressive Form of Chronic Lymphocytic Leukemia , 1999 .

[8]  Akt is activated in chronic lymphocytic leukemia cells and delivers a pro-survival signal: the therapeutic potential of Akt inhibition , 2010, Haematologica.

[9]  J. Whittaker,et al.  Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival , 1997, Leukemia.

[10]  C. Croce,et al.  Karyotype-specific microRNA signature in chronic lymphocytic leukemia. , 2009, Blood.

[11]  Anil Potti,et al.  A Genomic Approach to Improve Prognosis and Predict Therapeutic Response in Chronic Lymphocytic Leukemia , 2009, Clinical Cancer Research.

[12]  H. Döhner,et al.  Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia , 2010, Haematologica.

[13]  T. Naoe,et al.  Prospective monitoring of BCR‐ABL1 transcript levels in patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia undergoing imatinib‐combined chemotherapy , 2008, British journal of haematology.

[14]  H. Döhner,et al.  Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. , 2005, Blood.

[15]  G. Lenz,et al.  Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph^+ALL) , 2006 .

[16]  J. Radich,et al.  Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. , 2007, Blood.

[17]  J. Oldenburg,et al.  Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). , 2007, Blood.

[18]  M. Stratton,et al.  The cancer genome , 2009, Nature.

[19]  Arthur Weiss,et al.  ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. , 2004, The New England journal of medicine.

[20]  Muller Fabbri,et al.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. , 2005, The New England journal of medicine.

[21]  Göran Roos,et al.  Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia. , 2002, Blood.

[22]  Michael Hallek,et al.  miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia. , 2009, Blood.

[23]  N. Heerema,et al.  Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Susan O'Brien,et al.  De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience. , 2008, Blood.

[25]  Axel Benner,et al.  Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival , 2007, Haematologica.

[26]  N. Chiorazzi,et al.  Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. , 1999, Blood.

[27]  Emili Montserrat,et al.  ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. , 2003, The New England journal of medicine.

[28]  Yoo-Jin Kim,et al.  Risk factors for adults with Philadelphia‐chromosome‐positive acute lymphoblastic leukaemia in remission treated with allogeneic bone marrow transplantation: the potential of real‐time quantitative reverse‐transcription polymerase chain reaction , 2003, British journal of haematology.

[29]  T. Shanafelt,et al.  Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  K. Coombes,et al.  Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens. , 2009, Blood.

[31]  J. Hirschhorn Genomewide association studies--illuminating biologic pathways. , 2009, The New England journal of medicine.

[32]  D. Rossi,et al.  The Prognostic Value of TP53 Mutations in Chronic Lymphocytic Leukemia Is Independent of Del17p13: Implications for Overall Survival and Chemorefractoriness , 2009, Clinical Cancer Research.

[33]  Marcos González,et al.  Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis , 2008, British journal of haematology.

[34]  C. Mayr,et al.  Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia. , 2006, Blood.

[35]  C. Croce,et al.  MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Axel Benner,et al.  Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. , 2008, Blood.

[37]  L. Bullinger,et al.  Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia , 1999, Leukemia.