title: Phenotypic and genotypic switch in Philadelphia-positive, BCR-positive blast crisis of chronic myeloid leukemia.
abstract: We report a case of Ph1-positive, bcr-positive chronic myeloid leukemia blast crisis (CML-BC) which at presentation showed a mixed myeloid/B-lymphoid immunophenotype along with TdT positivity and, at the molecular level, an oligoclonal rearrangement of the immunoglobulin heavy chain (IgH) gene region. After obtaining a successful remission, at the time of relapse the patient underwent a phenotypic and genotypic switch from mixed to myeloid phenotype, characterized by the loss of the lymphoid markers and TdT expression and by a germline configuration of the IgH gene region. The same bcr rearrangement was, however, found in both phases of the disease, supporting the suggestion of a true phenotypic and genotypic conversion. This report confirms that the neoplastic event in CML may take place at an early multipotent stem-cell level, prior to a well-defined phenotypic and genotypic lineage expression. Moreover, it is suggested that different factors (chemotherapy? growth factors?) may have either eradicated the bcr+/IgH+ clone and promoted the growth of bcr+/IgH- leukemic cells or, alternatively, supported the lymphoid differentiation program and induced a myeloid lineage shift.
authors.affiliation: Divisione di Ematologia, Ospedali Riuniti, USL n. 31, Reggio Calabria, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Callea
authors.forename: F
authors.initials: F
authors.lastname: Morabito
authors.forename: P
authors.initials: P
authors.lastname: Francia di Celle
authors.forename: F
authors.initials: F
authors.lastname: Ronco
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: F
authors.initials: F
authors.lastname: Nobile
authors.forename: R
authors.initials: R
authors.lastname: Foa
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D015152:Blotting, Northern; D004247:DNA / Q000032:analysis; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr; D012008:Recurrence
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D011518:Proto-Oncogene Proteins; D004247:DNA; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr