Acute lymphoblastic leukemia (ALL) is a malignant disease of the bone marrow, characterized by the proliferation of lymphoid precursor cells. These precursor cells increase to a large enough number that cause a replacement of the normal bone marrow elements, causing anemia, thrombocytopenia, and neutropenia. Proliferation of the lymphoblasts also occurs in the liver, spleen, lymph nodes, and other organs. ALL is the most common type of pediatric cancer. The major cause of this cancer is thought to be exposure to high levels of radiation and/or carcinogens, such as benzene. About 5% of ALL cases are due to related genetic disorders, such as Down's syndrome. Chromosomal rearrangements are the causative factor in a majority of the cases.
A confirmed diagnosis of ALL requires the visualization of the abnormal proliferation of lymphocytes in the blood and bone marrow samples. This test is also used to categorize ALL into types. Lumbar punctures are used to detect the presence of leukemic cells in the CSF. Patients are usually treated with a combination of chemotherapy, radiation therapy, and if necessary, a bone marrow transplant. Surgery is not an option for ALL. The chemotherapy itself is administered in three phases; remission induction, intensification, and maintenance phases. The prognosis depends upon the type of leukemia. Current treatment modalities predict only a 20-40% of survival rate among adults. The prognosis for children, however, is better.
As mentioned earlier, a few cases of ALL are associated with genetic conditions, such as Down syndrome, Fanconi anemia, and Bloom syndrome. Cytogenetic abnormalities, specifically chromosomal translocations are more common. The most well-known example of this is the Philadelphia translocation, t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein that causes an upregulation of the ABL tyrosinase kinase activity. Another common translocation, especially among pediatric ALL cases, is the t(1;19)(q23;p13) rearrangement that results in a E2A-PBX fusion. Translocations implicated in ALL result in the TEL-AML1 and the MLL-A4 fusion proteins. In addition, two novel susceptibility loci for ALL have been recently mapped to 10q21 and 7p12.2.
Al-Husseinawi (2014) evaluated the frequency of FLT3-ITD mutation in acute lymphoid leukemia (ALL) patients using conventional polymerase chain reaction (PCR). The study included 25 individuals (16 children with ALL and nine adults with ALL), attending two teaching hospitals in Baghdad. FLT3-ITD mutation was detected in two patients. These cases were an 8-year-old girl and a 7-year-old boy, L2 subtype, who had achieved complete hematological remission throughout the study.
Al-Bahar et al. (1994) studied the occurrence of leukemia subtypes in Kuwait between 1979 and 1989. In their study, ALL was found to be the most frequent subtype, with 44.2% of the 723 cases being attributed to it. ALL was also found to be the most common pediatric leukemia in this population, and was found to exhibit a peak incidence at 0-4 years age group.
Zamecnikova and Al Bahar (2009) reported the case of a 4-year old male patient with ALL in Kuwait. Chromosome analysis on bone marrow aspirate showed a three-way translocation t(5;11;17)(q31;q23;q21) along with isochromosome of 7q and deletion of 12p. Further FISH studies revealed that the MLL gene was partly translocated to the derivative chromosome 17, with residual N-terminal segments remaining at 11q23 where it fused with C-terminal segments of a gene from 5q31. The probes confirmed the simultaneous occurrence of a 5q31/RARA fusion on chromosome 5q, a RARA/MLL fusion on chromosome 17, and a putative MLL/5q31 fusion at 11q23. This was the first described case of translocation of RARA to 5q31 in pediatric ALL. Following chemotherapy achieving complete cytogenetic remission, the patient succumbed to septicemia.
Elyamany et al. (2014) analyzed the prevalence of activating ITD and point mutations in the FLT3 gene in a sample of 77 patients with ALL in Saudi Arabia and tried to assess their prognostic significance. Only two of the 77 patients examined showed FLT3 mutations, giving an overall prevalence of 3%. Both patients responded well to treatment and achieved complete remission. Elyamany et al. (2014) concluded that there was no prognostic significance of FLT3 mutations in ALL patients.
Siddiqui et al. (2010) conducted a study to identify ALL-specific fusion genes (ETV6-RUNX1, MLL-AF4, TCF3-PBX1, and BCR-ABL1) in 181 children with newly diagnosed ALL from India, Pakistan, Myanmar, and Sudan. Across the four countries, the ETV6-RUNX1 (TEL-AML1) fusion gene was present in only 5% of cases. All the positive samples were from children aged 1 to 10 years, in whom the prevalence of this fusion gene, which is associated with good prognosis, was 7.4% (9 out of 121 samples), a much lower rate than reported from Western populations. In the 18 ALL cases from Sudan, a notable excess of MLL-AF4 (17%) and BCR-ABL1 (22%) fusion genes was found.
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