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.

Association of TP53 gene polymorphisms with the risk of acute lymphoblastic leukemia in Moroccan children.

BACKGROUND: TP53 gene plays a pivotal role in maintaining genetic stability and prevention of malignancies. Alterations of this gene are implicated in more than half of human cancers. To the best of our knowledge, this study is the first to explore TP53 polymorphisms in Moroccan childhood acute lymphoblastic leukemia (ALL). METHODS AND RESULTS: DNA samples of 45 ALL children were obtained from peripheral blood. A total of 333 healthy Moroccans were used as controls. Polymerase chain reaction and Sanger sequencing were performed to analyze TP53 hotspot exons in cases. We identified a significant protective effect of the TP53-Arg variant at rs1042522 [OR 0.4593 (0.249-0.8472), p = 0.0127] and the Pro/Arg genotype [OR 0.0350 (0.0047-0.2583), p = 0.0010]. Additionally, we found a novel association between the C-allele of Arg213Arg 1800372 [OR 2.7736 (1.3821-5.5664), p = 0.0041] and the risk of childhood ALL. Importantly, TC/CC genotypes of this polymorphism were revealed to enhance the risk of ALL among females [OR 9.0 (3.1555-25.6693), p < 0.0001]. Arg213Arg was also noticed to be associated with the hemoglobin count of patients at diagnosis by linear regression (p = 0.0318). The analysis of penetrance showed a significant association of the CG/GG genotypes at rs1042522 and TC/CC genotypes at rs1800372 to childhood ALL via dominant model [OR 0.2090 (0.09074-0.4814), p = 0.0002 and OR 3.4205 (1.6084-7.2742), p = 0.0014 for rs1042522 and rs1800372 respectively]. No association was found between TP53 polymorphisms and patients survival. CONCLUSION: Altogether, our findings indicated that TP53 polymorphisms are significantly involved in the genetic susceptibility to childhood ALL in Morocco.

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.

A prognostic approach on a case of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia with monosomy-7.

In this work, we present the first case of a Ph-positive ALL Moroccan girl with t(9;22)(q34;q11) and monosomy-7. She was diagnosed with Ph-positive ALL based on bone marrow examination, immunophenotyping, and cytogenetic analysis. She relapsed after treatment with the persistence of the Ph chromosome and the appearance of a monosomy-7.

Cytogenetic and FISH analysis of 93 multiple myeloma Moroccan patients.

BACKGROUND: Multiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), performed on sorted plasma cells detected abnormalities independently of a proliferative and infiltrative index. The purpose of this study was to explore, for the first time, the cytogenetic and molecular genetics features in Moroccan patients with multiple myeloma referred exclusively to National Reference Laboratory and to determine their risk stratification based on these features. METHODS: We performed cytogenetic analysis on 93 MM cases, all patients were subjected to FISH analysis, among which 45 patients have benefited from both FISH analysis and standard karyotype. RESULTS: Karyotype was normal in 78% (35/45) while, it was complex with varied structural and numerical abnormalities in 22% (10/45) of all patients, among which Hyperdiploid karyotype was found in 9% (n = 4 cases) and nonhyperdiploid in 13% (n = 6 cases). The most common numerical abnormalities were gains of chromosomes 3, 5, 9, 15, and 19. Whole chromosome losses were also frequent, affecting chromosomes X, 3, 14, 16 and 22. FISH analysis detected abnormalities in 50% of cases. The translocation t(4;14) and dup (1q) were the most frequent types of anomalies (14% and 13% respectively), followed by (17p) deletion and 14q32/IGH translocations with an undetermined origin (12% each) then the (1p) deletion (4%). For the normal karyotypes, FISH revealed chromosome abnormalities in 46%. CONCLUSION: This study compares the results of cytogenetic analysis of chromosomal abnormalities in the Moroccan population with other countries. ½ patient showed at least one type of molecular genetic abnormalities. Therefore, the introducing of the cytogenetic analysis is obligatory in the diagnosis of multiple myeloma.

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.