title: Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases.
abstract: In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional phenomenon, whose biologic features are unknown. We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year follow-up, despite a residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of V(H)3-30 gene in 2. The light chain variable region genes were mutated in 6 of 8 cases, with the use of V(kappa)4-1 gene in 3. Microarray analysis of CLL cells showed a distinctive genomic profile with an overrepresentation of BCR-related and ribosomal genes, regulators of signal transduction and transcription. The number of activated T lymphocytes expressing IFN-gamma, TNF-alpha, and IL-4 was similar between CLL in spontaneous regression and healthy persons. In conclusion, spontaneous clinical regressions can occur in CLL despite the persistence of the neoplastic clone, and the biologic features include negative CD38 and ZAP-70, mutated V(H)3-30 and V(kappa)4-1 genes. The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression.
authors.affiliation: Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolaro
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Roberta
authors.initials: R
authors.lastname: Maggio
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.forename: Simona
authors.initials: S
authors.lastname: Santangelo
authors.forename: Marilisa
authors.initials: M
authors.lastname: Marinelli
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Mauro
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D002999:Clone Cells; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D005803:Genes, Immunoglobulin; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D012075:Remission, Spontaneous; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
chemical_list: D011947:Receptors, Antigen, B-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1