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Biomedical subjects

E Abdelhay

Publications and source records attributed to E Abdelhay.

18 recordsLinked to original sources
PubMed2000

Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia.

Several studies have demonstrated the prognostic value of cytogenetic analysis in MDS both for survival and progression to AML. However it is unknown which are the numerical or structural abnormalities required for leukemic transformation. In this report we studied clinically and cytogenetically 127 patients: 125 with primary MDS and two with AML with a previous history of MDS. Thirty-one patients (24%) showed evolution of the disease during the follow-up study. Chromosomal abnormalities found at diagnosis in patients that progressed toward AML included: del(5)(q15), +6, del(6)(q21), t(5;8)(q32;q22),-7, del(7)(q22), der(7)t(1;7)(q10;p10), t(7;11)(p15;p15), +8, del(11)(q23), del(12p), del(3)(q21), del(20)(q12) and complex karyotypes. Eight of these patients were studied cytogenetically during transformation and showed acquisition of chromosomal alterations involving dup(1q), +8, del(11)(q23), and translocations between chromosomes 1 and 8 or 7 and 17. In addition we also observed gain of ploidy and monosomy 21. These results suggest that chromosomal alterations during evolution of the disease include special chromosome gains or abnormalities of chromosomes 1, 7, 8, 11 and 17 with involvement of ETV-1, Hox-A9, Pax 4, MLL genes besides a putative gene mapped at 17q25. We also applied the International Prognostic Scoring System (IPSS) to 114 patients, excluding those submitted to allogeneic bone marrow transplant. Our patients were classified into four distinct risk groups. The analysis of risk groups presented by 27 patients who showed evolution of the disease revealed 18 at the high risk group and four at the intermediate-2 group. From the intermediate-1 risk group only five patients showed evolution of the disease. Three of these patients evolved from RA to RAEB with gain of a del(11)(q23) or an expansion of a del(12)(p12) clone. Our results suggest that some chromosomal alterations are responsible for each step in the evolution of the disease. As the pathway of evolution is not unique it has been very difficult to define what genetic alteration comes first. However from several results in the literature and our own, it seems that some chromosomal alterations may predict the evolution of the disease and are correlated with short survival, as for example the trisomy of chromosome 8, and might be incorporated in the high risk group in the IPSS. This score system has been proved to be useful for predicting survival and evolution from MDS to AML.

Adolescent↗
PubMed2000

Complex karyotype and N-RAS point mutation in a case of acute megakaryoblastic leukemia (M7) following a myelodysplastic syndrome.

The development of acute megakaryoblastic leukemia (ANLL-M7) following myelodysplastic syndrome (MDS) has been described only in a few reports, and the mutations necessary for this transformation are still unknown. In this study, we describe a case of ANLL-M7 with a previous history of MDS presenting a complex karyotype 46,XX, t(4;11)(q21;q23),del(5)(q13q33),t(12;13)(p13;q21) and N-RAS point mutation. During MDS, the patient showed a hypercellular myelogram with dysplasia of the three myeloid lineages and the clinical symptoms characteristic of the 5q- syndrome. During the follow-up, we observed the appearance of two additional subclones, one with an isochromosome 17q and another with polyploidy. The presence of an isochromosome 17q in one subclone and polyploidy in another is probably due to the genetic instability generated by the malignant transformation.

Chromosome Aberrations↗
PubMed1998

Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome.

A cytogenetic and N-ras point mutation study was done in patients with primary myelodysplastic syndrome (MDS) from Rio de Janeiro, Brazil, in order to evaluate the progression of preleukemic states to overt leukemia. Cytogenetic analysis was performed in 50 patients with MDS and clonal chromosomal abnormalities were detected in 19 (38%) of them. Patients with refractory anemia (RA) or with ringed sideroblasts (RARS) presented normal karyotypes or single abnormalities as del(5q) or -Y, while patients in more advanced states as RA with excess of blasts (RAEB), RAEB in transformation (RAEB-t) and chronic myelomonocytic leukemia (CMML) showed complex karyotypes and single abnormalities involving chromosomes 7 or 8, which were related to poor prognosis and elevated risk of transformation to acute myeloid leukemia (AML). The frequency of ras activation was studied in these 50 patients with MDS. Samples of bone marrow were screened for oncogenic point mutations by DNA amplification followed by oligonucleotide hybridization analysis (PCR-ASO) at codon 12 of N-ras proto-oncogene. We detected N-ras point mutations in 21 patients (42%). Progression from MDS to AML was observed in 9 patients (18%). The correlation analysis between N-ras point mutations and specific chromosomal abnormalities indicated that although mutated N-ras was found in cells with del(5q) and monosomy 7, cells with those abnormalities and normal N-ras were also identified. Otherwise trisomy of chromosome 8 showed a correlation with N-ras point mutations and in all cases, patients showed progression of MDS to AML during the follow-up study. MDS comprises a heterogeneous group of hematopoietic disorders and probably several steps are implicated in the evolution to AML. In this work we suggest that one possible pathway of leukemogenesis in MDS includes N-ras point mutations in association with trisomy of chromosome 8.

Adolescent↗
PubMed1998

Structural and functional analysis of mouse Msx1 gene promoter: sequence conservation with human MSX1 promoter points at potential regulatory elements.

Vertebrate Msx genes are related to one of the most divergent homeobox genes of Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well-defined pattern at sites of tissue interactions. This pattern of expression is conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of sites including neural crest, appendages, and craniofacial structures. In the present work, we performed structural and functional analyses in order to identify potential cis-acting elements that may be regulating Msx1 gene expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced and analyzed for transcription-factor binding sites. Four regions showing a high concentration of these sites were identified. Transfection assays with fragments of regulatory sequences driving the expression of the bacterial lacZ reporter gene showed that a region of 4 kb upstream of the transcription start site contains positive and negative elements responsible for controlling gene expression. Interestingly, a fragment of 130 bp seems to contain the minimal elements necessary for gene expression, as its removal completely abolishes gene expression in cultured cells. These results are reinforced by comparison of this region with the human Msx1 gene promoter, which shows extensive conservation, including many consensus binding sites, suggesting a regulatory role for them.

Animals↗
PubMed1995

Translocation 11;14 in three children with acute lymphoblastic leukemia of T-cell origin.

Clinical, karyotypic, immunophenotypic, and molecular profiles of three TALL cases carrying a t(11;14) are discussed and compared with data in the literature. As previously reported, t(11;14)(p13;q11) was associated in one patient with a TALL profile of intermediate stage of maturation (CD7+, CD4+, CD8+). However, the same translocation was found to be present in another patient with a more immature, pro-TALL profile (CD7+, CD4-, CD8-). Both patients showed molecular rearrangements of the TCR beta chain gene. A third patient, with a very immature pro-TALL profile (CD34+, CD7+, CD4-, CD8-), carrying a t(11;14)(p15;q11), showed molecular rearrangements of the TCR beta and gamma chain genes, while the IgH chain genes were in germline configuration. Our data indicate that t(11;14) can also be present in TALLs of more immature stages of intrathymic development; the significant factor determining the clinical behavior of TALLs is apparently related more to cell differentiation than to the presence of this chromosome rearrangement.

Adolescent↗
PubMed1995

Highly polymorphic repetitive sequences in Rhynchosciara americana genome.

Rhynchosciara americana genomic DNA when digested with EcoR1 or BamH1 presents visible fragments suggestive of repetitive sequences after fractionation on EtBr stained agarose gels. The cloning and molecular analysis of some of these fragments showed a highly polymorphic family of repetitive sequences. These were mapped by in situ hybridization to telomeres and some heterochromatic regions on polytene chromosomes.

Animals↗
PubMed1995

Analysis and in situ mapping of the Adh locus in species of the willistoni group of Drosophila.

The Adh locus was mapped by in situ hybridization with the heterologous biotinylated probe SAC-PAT to the salivary chromosomes of seven species of the willistoni group of Drosophila. Hybridization signals were obtained mainly at a single site to the right arm of chromosome II in six species, but in Drosophila nebulosa two sites hybridized with the same consistency. Southern blot analysis Eco RI-digested genomic DNA of the seven species revealed high molecular weight bands shared by three species, plus the appropriately sized fragment expected, suggesting the presence of Adh pseudogenes in those species.

Alcohol Dehydrogenase↗
PubMed1993

Translocation of CD3D gene in an acute myeloid leukemia (M5) with t(11;17)(q23;21).

Cytogenetic studies in patients with acute leukemia showed structural abnormalities on chromosome 11 at band q23 in five cases. Four of these had acute lymphoblastic leukemia (ALL) associated with t(4;11)(q21;q23) and one case had acute nonlymphoblastic leukemia (ANLL) (M5) associated with t(11;17)(q23;q21). We examined the CD3D and c-ets-1 genes in the t(11;17)(q23;q21) patient to ascertain any association between them and the chromosome change. In situ hybridization results showed that unlike in other studied cases with rearrangements of 11q23, the CD3D gene in the t(11;17)(q23;21) is transposed to the der(17) chromosome, providing evidence for a different breakpoint in the 11q23 region.

CD3 Complex↗
PubMed1993

Heat shock genes in the willistoni group of Drosophila: induced puffs and proteins.

Seven species of the willistoni group of Drosophila were comparatively analysed for their response to heat shock and anoxia, both at the transcriptional (induced puff) and translational (induced protein) levels. The number of induced puffs varied among the species, but were concentrated at chromosomes 3 and XR. One puff present under control (25 degrees C) conditions was found to increase in size in response to stress in all species. Proteins of 83 and 70 kD were induced in all species in response to heat shock, as well as proteins of 50 and 32 kD, but not reported for other species of Drosophila under similar conditions. The number and size of the small heat shock proteins induced, as expected, showed considerable interspecific variability.

Animals↗
PubMed1992

Late marrow allograft rejection following alpha-interferon therapy for hepatitis in a patient with paroxysmal nocturnal hemoglobinuria.

We describe a case of allograft rejection that occurred 23 months after successful bone marrow transplantation for severe aplastic anemia in a patient with paroxysmal nocturnal hemoglobinuria. The allograft rejection appears to have been induced by recombinant alpha-interferon (rINF-alpha) treatment for non-A, non-B hepatitis that developed 11 months after transplantation. During the 9 months of active hepatitis, the donor graft functioned normally; however, 3 months after rINF-alpha therapy was started, pancytopenia and a chimeric hematopoietic state developed. rINF-alpha was discontinued, cyclosporin A was reintroduced, and autologous bone marrow recovery followed. rINF-alpha treatment may be detrimental to some recipients of allogeneic bone marrow transplants.

Adult↗
PubMed1991

CD7+, CD4-/CD8- acute leukemia with t(11;14)(p15;q11) in a child.

A t(11;14)(p15;q11) was the sole chromosome abnormality observed in the malignant cells of a 10-year-old boy with acute leukemia. Morphologically, these cells were classified as L1 by the criteria of the French-American-British Working Group. Cytochemical analysis revealed that the leukemic cells were negative for Sudan Black B, periodic acid Schiff, and esterases, and positive for acid phosphatase. Immunophenotyping disclosed that the cells expressed a very immature antigenic profile [CD34+, CD7+, cytoplasmic CD3+, membrane CD3-, CD4-, and CD8-]. In spite of very intensive chemotherapy, complete remission was never induced, and the child died of progressive disease. The relationship of this case to other reported cases of acute leukemia arising from immature pluripotent hematopoietic cells is discussed.

Antigens, CD↗
PubMed1991

Transcription in Rhynchosciara americana embryos' early development.

Embryonic transcription starts about 6 hr postfertilization and increases during the first 72 hr of development. During this stage rRNA is the most abundant transcript, but some premessenger RNAs are also present. At 96 hr of development poly(A+) mRNA starts to be detected concordant with gastrulation movements.

Animals↗
PubMedDate not supplied

Genomic distribution of P elements in Drosophila willistoni and a search for their relationship with chromosomal inversions.

According to the recent-invasion hypothesis, Drosophila melanogaster may have acquired its P elements in a fairly recent process of horizontal transmission between species. Drosophila willistoni has been identified as the potential donor species in that transfer process. A most remarkable feature of D. willistoni is its extensive chromosomal polymorphism due to inversions-the adaptiveness of which has been the subject of many classical studies on evolutionary genetics. In this article, we further extend the study of P elements in D. willistoni, focusing on the possible role they may play in the generation of chromosomal inversions. Our results may be summarized as follows. P-homologous sequences were detected in South American populations of D. willistoni. In two of them, a recently collected wild population and an old laboratory stock, the P insertion sites were located in the polytene chromosomes. Several hybridization sites were mapped in all major chromosome arms of the natural population, which was also chromosomally polymorphic; in the laboratory population, nearly devoid of inversions, hybridization sites were found to be confined to the chromocenter. In the wild population, 10 of the 24 P hybridized sites coincided with several inversions break points and another five sites located themselves very close to those points. The results are discussed within the context of evolutionary hypotheses.

Animals↗