RESUMEN
Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome (IBMFS). Affected individuals must be distinguished from relatives, patients with mosaicism must be identified, and patients with other IBMFS classified as non-FA. The diagnostic feature of FA is increased chromosomal breakage in blood lymphocytes cultured with diepoxybutane or mitomycin C. Here, we sought a method to uniquely identify patients with FA with mosaicism, using cells from participants in the National Cancer Institute IBMFS cohort. Lymphocytes were treated with diepoxybutane or mitomycin C, and metaphases scored for breaks and radials. Analyses included the percentage of cells with any aberration, breaks per cell, and breaks per aberrant cell. There were 26 patients with FA (4 mosaics), 46 FA relatives, and 62 patients with a non-FA IBMFS. By all analytic methods, patients with FA were abnormal compared with other groups. Those with FA mosaicism had more breakage than relatives or patients with non-FA IBMFS, but there was some individual overlap. The choices of clastogen are laboratory-dependent, but there was no method or analysis of lymphocytes that clearly distinguished all individuals mosaic for FA from relatives or patients with other IBMFS. Thus, genotyping remains the best method for providing absolute clarity.
Asunto(s)
Rotura Cromosómica , Anemia de Fanconi/genética , Hemoglobinuria Paroxística/genética , Mosaicismo , Adolescente , Adulto , Anciano , Anemia Aplásica , Enfermedades de la Médula Ósea , Trastornos de Fallo de la Médula Ósea , Niño , Preescolar , Estudios de Cohortes , Compuestos Epoxi/farmacología , Femenino , Tamización de Portadores Genéticos , Genotipo , Humanos , Lactante , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mitomicina/farmacología , Mutágenos/farmacología , Adulto JovenRESUMEN
Specific cytogenetic clones might distinguish patients with unrecognized Fanconi anemia (FA) who present with acute myeloid leukemia (AML) from those with sporadic AML. Cytogenetic reports in literature cases of FA and AML were compared with de novo cases enrolled on CCG-2961. Gain of 1q, gain of 3q, monosomy 7, deleted 7q, gain of 13q, and deleted 20q were more frequent in FA AML; t(8;21), trisomy 8, t(9;11), t(6;9), and inversion 16 were exclusive to de novo AML cases. Observation of the FA AML cytogenetic clonal patterns should raise suspicion of an underlying leukemia predisposition syndrome and influence management.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos/genética , Anemia de Fanconi/genética , Anemia de Fanconi/terapia , Predisposición Genética a la Enfermedad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Niño , Preescolar , Anemia de Fanconi/complicaciones , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/complicaciones , MasculinoRESUMEN
We speculated that some individuals with de novo acute myelogenous leukemia (AML) may have undiagnosed Fanconi Anemia (FA). Data from patients enrolled on AML protocol CCG-2961, published FA cohort studies, SEER, and Bayes rule were used to estimate the probability of FA among all newly diagnosed AML cases, and among those who had no or delayed recovery of the absolute neutrophil count following initial chemotherapy. We determined that the probability of undiagnosed FA in patients in a treatment trial for newly diagnosed patients was around 0.18%, and around 0.83% in the subset who had poor marrow recovery. We suggest that FA or other inherited bone marrow failure syndromes be considered prior to treatment, or certainly among those with poor recovery.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anemia de Fanconi/complicaciones , Anemia de Fanconi/epidemiología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Estudios de Cohortes , Diagnóstico Tardío , Anemia de Fanconi/diagnóstico , Humanos , Leucemia Mieloide Aguda/rehabilitación , Prevalencia , Recuperación de la Función , Factores de TiempoRESUMEN
BACKGROUND: The inherited bone marrow failure syndromes (IBMFS) include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome (SDS). Previous studies reported decreased neutrophil chemotaxis in patients with SDS; there are no reports of neutrophil function in other IBMFS. In this study we examined neutrophil respiratory burst function in IBMFS patients. PROCEDURE: Samples from 43 IBMFS patients and 61 healthy family members were collected, shipped, and analyzed within 24 hr. We also studied samples from 12 healthy control persons immediately after collection. Neutrophils were stimulated with phorbol 12-myristate acetate (PMA) and N-formyl-methyonyl-leucyl-phenylalanine (fMLP), and respiratory burst analyzed by reduction of dihydro-rhodamine and cytochrome c. RESULTS: There was no significant difference in the degree of fMLP or PMA-driven respiratory burst activity between each of the IBMFS subgroups and their respective family members. There was also no difference in respiratory burst activity between any IBMFS, pooled group of all healthy family members and healthy controls. CONCLUSIONS: Neutrophil respiratory burst activity from IBMFS patients does not differ from that of healthy family members and controls.