ABSTRACT
Monosomal karyotype (MK) has recently been reported to identify a distinct subset of acute myeloid leukemia (AML) with adverse prognosis. We retrospectively evaluated the frequency of MK in a large cohort of 549 unselected AML cases diagnosed in our department over a period of 13 years and explored potential associations with clinicobiological features and outcome. MK was found in 62 of 549 cases (11.3%), with all but one assigned to the unfavorable cytogenetic risk category; 57 of these 62 MK cases had a complex karyotype. Comparison with a subgroup of AML cases, who had unfavorable karyotypic profiles yet without MK (non-MK) and who were treated uniformly with similar, "3+7"-based regimens, revealed significant (P < 0.05) associations between MK and advanced age, low white blood cell count at diagnosis, and inferior overall survival (6.5 vs. 15 months for non-MK cases). In conclusion, MK defines a sizeable subset of patients with unfavorable cytogenetics who exhibit a distinct clinical profile, even in direct comparison with other unfavorable karyotypes.
Subject(s)
Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/diagnosis , Monosomy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cytogenetics , Female , Humans , Karyotype , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Monosomy/diagnosis , Prognosis , Retrospective Studies , Risk , Survival Analysis , Young AdultSubject(s)
Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 21/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Oncogene Proteins, Fusion/genetics , Repressor Proteins/genetics , Translocation, Genetic/genetics , Tumor Suppressor Proteins/genetics , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Prognosis , Young AdultSubject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Translocation, Genetic , Adult , Antineoplastic Agents/adverse effects , Benzamides , Clonal Evolution , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Philadelphia Chromosome , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Remission InductionABSTRACT
We report a remarkable association of recurrent (stereotyped) cytogenetic aberrations with two subsets of chronic lymphocytic leukemia (CLL) cases expressing IgG-switched, stereotyped B-cell receptors (BCRs). Comparison with cases with heterogeneous BCRs showed that these recurrent cytogenetic aberrations were subset-biased. These findings further support a role for antigen in CLL development.
Subject(s)
Chromosome Aberrations , Complementarity Determining Regions/genetics , Immunoglobulin G/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Neoplasm Proteins/genetics , Receptors, Antigen, B-Cell/genetics , Humans , Immunoglobulin Switch Region , Leukemia, Lymphocytic, Chronic, B-Cell/classification , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/pathologyABSTRACT
In a cohort of 130 unselected chronic lymphocytic leukemia (CLL) patients, 73 cases had normal karyotypes, 57 cases had abnormal karyotypes, and 22/57 cases carried more than one abnormality. Trisomy 12 (+12) was the most common abnormality (26/130 cases; 20%), and 17/26 cases had isolated +12. Del(13q)/t13q/-13 was detected in 19/130 cases (14.6%), and 5/19 cases had isolated del(13)(q12q14). Deletion (11)(q23) and del(17p)/-17 were detected in 5/130 cases, respectively. CD38 expression was significantly more frequent in the +12/11q/17p versus the normal/del(13q) subgroups. A significant association was detected between +12 and FMC7 positivity. IGHV-unmutated cases were significantly more frequent in the +12/11q/17p subgroups. Patients with normal karyotype/del(13q) had a longer median time to progression versus the patients in the +12/11q/17p subgroups. According to multivariate analysis, only IGHV mutation status remained a statistically significant variable for progression-free survival (PFS). Furthermore, IGHV mutation status and clinical stage at diagnosis were the only significant prognostic factors for overall survival. Among Binet-A patients, significant parameters for shorter PFS were +12 or 11q/17p aberrations, CD38 expression, and IGHV unmutated status. In multivariate analysis, only CD38 expression and IGHV-unmutated status retained statistical significance for PFS. In conclusion, trisomy 12 in CLL is characterized by considerable heterogeneity and seems to be associated with disease progression.