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The chromosomal translocation t(8;14)(q24;q32) represents a characteristic marker for Burkitt's lymphoma (BL). This translocation involves the MYC oncogene on chromosome 8 and the immunoglobulin heavy-chain (IgH) locus on chromosome 14. Since the translocation does not produce a fusion gene, we established a long-distance polymerase chain reaction (LDPCR) assay that can detect the t(8;14) at the genomic level. The sensitivity of the LD-PCR was 10[sup -4]. We used the LD-PCR assay to prospectively study 78 BL patients and found a specific PCR product in 52 of them. Among the 52 positive patients, we could test both the tumor and the bone marrow (BM) at diagnosis in 33 and determined the prevalence of minimal disseminated disease (MDD) at diagnosis. In 12/33 patients, BM was positive by LD-PCR and in 10 of them we conducted a study of minimal residual disease (MRD). Eight out of 10 children showed a clearance of MRD after one cycle of chemotherapy. The only two patients who did not achieve a negative MRD status died of disease progression. The comparative analysis of sensitivity of BM aspirate, BM biopsy and LD-PCR in t(8;14)-positive patients demonstrated a superiority of the molecular method in the assessment of MDD. The LD-PCR for t(8;14) is an important tool to study minimal BM infiltration at diagnosis and to determine its response kinetics in BL. [ABSTRACT FROM AUTHOR]

Studies the dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH). Lack of evidence for intrinsic growth advantage of PNH clones; Patient selection and characteristics; Analysis of temporal trends; Fate of PNH cell populations over time; Pathophysiology.

Paroxysmal nocturnal haemoglobinuria (PNH) is a unique disorder characterised by the triad of intravascular haemolysis, thrombosis and bone marrow failure. In the early seventies it was shown that PNH is a clonal disease; and in the nineties the molecular basis of the PNH abnormality was elucidated. However, what makes a PNH clone expand is still not known. Here, we suggest that this is due to somatic cell selection, resulting from the presence in the patient of autoreactive T cells that target glycosylphosphatidylinositol (GPI) in the context of an MHC-like molecule on the surface of haemopoietic stem cells. PNH cells would escape damage precisely because they have lost most or all of their ability to produce GPI. [ABSTRACT FROM AUTHOR]

Glucose 6-phosphate dehydrogenase (G6PD) activity was assayed quantitatively in red cells from 100 consecutive G6PD-deficient newborn male babies born in a city hospital in Sassari, Sardinia. In four cases G6PD activity was between 30% and 45% of normal: these appeared on electrophoresis to be identical with G6PD Seattle-like. In 65 cases G6PD activity ranged from 2% to 14% of normal, while in the remaining 31 samples no activity could be detected in crude hemolysates. G6PD was partiall purified from 39 samples having activity below 14% of normal (including 20 with zero activity). G6PD activity could now be determined in all, and it was fully characterized in nine samples. These were shown to belong to two distinct classes on grounds of the Michaelis constant for glucose 6-phosphate and the elution profile from DEAE-Sephadex columns. These properties were compared with those of G6PD-deficient samples from Greece and from Israel. We conclude that there are at least three polymorphic G6PD-deficient variants in Northern Sardinia: G6PD Seattle-like, G6PD Mediterranean, and a new variant, which we designate G6PD Sassari. The Gd and Gd genes have been shown to breed true in family studies. We also produce evidence that the definition of G6PD Mediterranean must be carefully reassessed. [ABSTRACT FROM AUTHOR]

Focuses on the use of gene therapy in the treatment of human diseases. Technology needed for gene transfer; Gene therapy as an offshoot of understanding the molecular biology of inherited diseases; Prospects for adoptive cell therapies.

As part of a study aiming to define the molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency, we analysed a sample from a Portugese boy with a family history of favism. Although the biochemical properties of red-cell G6PD from this subject were similar to those of the common variant G6PD Mediterranean, the corresponding mutation (563 C→T) was not present. Instead, polymerase chain reaction (PCR) amplification and sequencing of the entire gene detected a C→T transition at nucleotide 592 in exon VI, changing an arginine residue to a cysteine residue only 10 amino acids downstream from the Mediterranean mutation. Single-strand conformation polymorphism analysis of a PCR-amplified DNA fragment spanning exons VI and VII of the G6PD gene has detected the same mutation, confirmed by sequencing, in a G6PD-deficient patient from Southern Italy. We name this new variant G6PD Coimbra. [ABSTRACT FROM AUTHOR]

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A letter to the editor is presented in response to the article on malaria resistance against plasmodium falciparum yielded by G6PD deficiency in the October 19, 2011 issue.