Cytogenetic abnormalities and TP53 and RAS gene profiles of childhood acute lymphoblastic leukemia in Morocco.

BACKGROUND: Recurrent genetic abnormalities affecting pivotal signaling pathways are the hallmark of childhood acute lymphoblastic leukemia (ALL). The identification of these aberrations remains clinically important. Therefore, we sought to determine the cytogenetic profile and the mutational status of TP53 and RAS genes among Moroccan childhood cases of ALL. METHODS: In total, 35 patients with childhood ALL were enrolled in the study. The diagnosis and treatment were established in the Pediatric Hematology and Oncology Center at the Children's Hospital of Rabat. Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Blood samples were screened for TP53 and RAS mutations using Sanger sequencing. RESULTS: Of the 35 cases, 30 were B-lineage ALL (85.7 %). Moreover, a male predominance was observed. Cytogenetic analysis revealed chromosomal anomalies in 27 cases (77.1 %). The most frequent aberrations were high hyperdiploidy and BCR/ABL rearrangement. Interestingly, we found the rare t(15;16) and the t(8;14), which are uncommon translocations in pediatric B-ALL. The mutational analysis revealed Pro72Arg (rs1042522:C > G) and Arg213Arg (rs1800372:A > G) in TP53. In correlation with cytogenetic data, rs1042522:C > G showed a significant association with the occurrence of chromosomal translocations (p = 0.04). However, no variant was detected in NRAS and KRAS genes. CONCLUSION: Our findings emphasize the significance of detecting chromosomal abnormalities as relevant prognostic markers. We also suggest a low occurrence of genetic variants among Moroccan children with ALL.

B/T mixed phenotype acute leukemia with high hyperdiploidy and lineage switch to B-cell acute leukemia.

Acute leukemias are often of myeloid or lymphoid origin. However, some acute leukemias revealed an undefined differentiation into a single lineage. Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis were blasts can share B/T/myeloid phenotype. Here, we report a rare case of a 17-year-old Moroccan female diagnosed with B/T mixed phenotype acute leukemia and a high hyperdiploid karyotype who relapsed after one year of complete remission with a lineage switch to B-cell acute lymphoblastic leukemia. This case report corroborates the disclosed findings about the high occurence of abnormal karyotypes and poor prognosis of MPAL.

Cytogenetic Profile of Moroccan Pediatric Acute Lymphoblastic Leukemia: Analysis of 155 Cases With a Review of the Literature.

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.