ABSTRACT
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with a peak incidence at 2 to 3 years of age and accounting for almost 30% of all cancers in this age group. It is well established that the identification of cytogenetic abnormalities is highly relevant for the prognosis of and therapeutic decisions in ALL. The purpose of the present study was to define the frequency of recurrent chromosomal abnormalities of ALL in Moroccan patients referred exclusively to the BIOLAB Laboratory of the Children's Hospital of Rabat during a 4-year period and compare our findings to the reported data. PATIENTS AND METHODS: We performed conventional karyotyping of 155 ALL cases, with a successful cell culture rate of 94%. RESULTS: We identified chromosomal abnormalities in 66% of the total studied cases, of which 70% revealed important recurrent abnormalities with high prognostic value, such as hyperdiploidy, hypodiploidy, t(9;22), t(8;14), t(1;19), and MLL rearrangements. In total agreement with the reported data, most of the patients (56%) in the present study were aged 1 to 5 years, with a male predominance, and B-ALL was the most common blast phenotype (85%). CONCLUSION: The frequency of most chromosomal rearrangements successfully identified in our study and their lineage correlated with those reported in the published data.
Subject(s)
Chromosome Aberrations/statistics & numerical data , Karyotyping/statistics & numerical data , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Age Distribution , Age Factors , Bone Marrow/pathology , Bone Marrow Cells , Child , Child, Preschool , Disease Progression , Female , Humans , Infant , Karyotyping/methods , Male , Morocco , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Retrospective Studies , Sex Factors , Tumor Cells, CulturedABSTRACT
Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information.
