Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study.

BACKGROUND: Screening of ß thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of ß thalassemia carriers and iron deficiency anemia among relatives of ß thalassemia patients in Mid Delta, Egypt. METHODS: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with ß thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. RESULTS: The total prevalence of iron deficiency anemia among close relatives of confirmed ß thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al-Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al-Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). ß thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). CONCLUSION: More than one-third of relatives of patients with ß thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with ß thalassemia in Egypt.

The prognostic impact of loss of chromosome 7 material detected by fluorescence in situ hybridization (FISH) in myeloid malignancies.

BACKGROUND: Monosomy 7 (-7) or deletion in its long arm [del(7q)] is among the most common chromosomal abnormalities in myeloid malignancies. There are prognostic variations between -7 and del(7q) in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). AIM: To describe the clinical characteristics, response to treatment, and survival of patients with primary AML and MDS having -7 or del(7q) detected by fluorescence in situ hybridization (FISH). PATIENTS AND METHODS: The study was conducted on 53 patients with primary AML and MDS. They were tested for chromosome 7 abnormality using FISH technique. RESULTS: Thirty-one patients had chromosome 7 abnormality and 22 did not. Lower complete remission and higher death rates were observed in patients with -7 (47.6% and 62%, respectively) when compared to patients with del(7q) (70% and 40%, respectively) with no significant difference (p = 0.218 and 0.101, respectively). The median overall survival (OS) of patients with -7, del(7q) and normal chromosome 7 were 32.0, 43.0 and 50.0 months, respectively, with significant statistical difference (p = 0.001). This difference was evident between patients with -7 and those with normal chromosome 7 (p = 0.001), and less evident between patients with -7 and those with del(7q) (p = 0.021). CONCLUSION: Chromosome 7 analysis has clear impact on the outcome of myeloid malignancies. The prognostic variations between -7 and del(7q) is attributed to multiple factors. Cases with del(7q) have better outcome than cases with -7. FISH provides a powerful tool for detecting and monitoring patients with chromosome 7 abnormalities.

A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.

The AML1 gene (also known as RUNX1 or CBFA2), located in chromosome band 21q22, encodes a transcription factor which heterodimerizes with the CBFbeta protein forming a complex called human core binding factor (CBF). The CBF complex appears to regulate a number of genes important for hematopoiesis. AML1 is one of the most common targets of chromosomal rearrangements in human leukemias and has been involved in 14 chromosomal translocations to date. Here we report a new chromosomal translocation, t(4;21)(q31;q22) that disrupts the AML1 gene in a 12-year-old boy with newly diagnosed T-cell acute lymphoblastic leukemia (ALL). This is the first reported chromosomal translocation where AML1 is rearranged in childhood T-cell ALL. By metaphase fluorescence in situ hybridization analysis, the AML1 breakpoint was mapped using recombinant phage clones, and shown to be either immediately upstream or downstream of exon 5.

Telomerase activity in Philadelphia positive chronic myeloid leukaemia.

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Chronic Myeloid Leukaemia (CML) is a good example to investigate the reactivation of telomerase as; after a variable period in chronic phase, CML undergoes further evolution. The aim of this work is to study telomerase activity in patients with philadelphia- positive CML and to compare the relative amount of telomerase activity between chronic phase, accelerated phase and blastic crisis. The study is conducted on 3 groups. Group I comprised ten newly diagnosed CML patients in chronic phase; five males and five females their ages ranged from 24-63 years (X = 44.1 +/- 11.2 years). Group II comprised ten patients in acute transformation (accelerated or blastic crisis phase); seven were males and three were females their ages ranged from 14 to 63 years ( X = 35.7 +/- 16.2 years). Ten healthy subjects comprised the control group III; five males and five females their ages ranged from 14-50 years ( X = 31.8 +/- 12.4 years). All patients were subjected to thorough history taking and clinical examination, complete blood picture with differential cell counts, bone marrow aspiration and/or biopsy, neutrophil alkaline phosphatase scoring by cytochemistry, immunophenotyping to identify the type of blast crisis, chromosomal analysis to detect Ph-positive cases, and measurement of telomerase activity by PCR-ELISA technique. Telomerase activity was highest in acute transformation with a range of (0.252-1.896) and mean of 1.521 0.496, while in chronic phase ranged between 0.67 and 0.743 with a mean of 0.305 +/- 0.109 and in normal controls the range was 0.45 to 0.195 with a mean of 0.102 +/- 0.048. The difference between groups was statistically significant. No correlation was found between the activity of the telomerase and hemoglobin, platelet, leucocyte counts, percentage of peripheral blood, bone marrow blasts, basophils, bone marrow cellularity, the type of crisis as well as leucocyte alkaline phosphatase scoring. In conclusion; The increased level of telomerase activity as noticed in the different stages of CML indicates its association with disease progression and can be used as a useful marker for evaluating development of the course.

A novel gene, FGA7, is fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient with T-cell acute lymphoblastic leukemia.

AML1 is among the most frequent targets of chromosomal rearrangements in human leukemias. We report here the molecular analysis of a t(4;21)(q28;q22) that has disrupted AML1 in a patient with de novo T-cell acute lymphoblastic leukemia. By using 3'-RACE analysis, we show that this rearrangement results in the fusion of a novel gene immediately downstream of exon 5 or exon 6 of AML1, indicating that the AML1 breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The sequence of the novel gene, located at 4q28, does not have any significant homology with any of the known genes in the human GenBank DNA database. However, the first 118 bases are identical to a part of a human ovarian EST. Also, its high homology with mouse and rat sequences suggests that this sequence most probably represents a part of a novel gene, which we named FGA7 (Fused Gene 7 to AML1). Following the AML1 open reading frame, the FGA7 sequence encodes an unknown protein of 27 amino acids. We isolated three bacterial artificial chromosome (BAC) clones that contain the FGA7 sequence and confirmed the breakpoint of the gene on the patient's metaphase spreads by fluorescence in situ hybridization using these BACs as probes. RT-PCR and Northern blot analyses revealed that FGA7 is expressed in ovarian and skeletal muscle tissues. The predicted AML1-FGA7 chimeric proteins contained a limited number of residues fused to AML1 in a situation similar to that reported for the AML1-EAP fusion that is a product of t(3;21). It is possible that the expression of a constitutively shortened AML1 could compete with full-length AML1 and act as a dominant negative inhibitor of the promoters that the core binding factor activates.