PubMed Health⌕ Search

Biomedical subjects

H Mossafa

Publications and source records attributed to H Mossafa.

18 recordsLinked to original sources

No BCL-2 protein over expression but BCL-2/IgH rearrangements in B cells of patients with persistent polyclonal B-cell lymphocytosis.

INTRODUCTION: Persistent polyclonal B-cell lymphocytosis is a rare hematological disorder, characterized by a chronic, stable and absolute polyclonal lymphocytosis, the presence of binucleated lymphocytes, a polyclonal increase in serum IgM immunoglobulin and clonal cytogenetic abnormalities involving chromosome 3. For explaining the expansion of B-lymphocytes pool in PPBL, an association with cigarette smoking and/or chronic Epstein-Barr virus infection have been suggested but both hypotheses have been ruled out. MATERIALS AND METHODS: We studied the presence of BCL-2/IgH rearrangements in a series of eight PPBL patients (seven females and one male) by a nested polymerase chain reaction (PCR), targeting the Major Breakpoint Region in BCL-2 locus and we explored the BCL-2 protein expression by Western blot. RESULTS: We demonstrated: (a) the constant presence of BCL-2/IgH rearrangements in eight out of eight DNA samples, (b) multiple rearrangements in three out of eight cases and, (c) normal BCL-2 protein expression, as compared to BCL-2 level in B-lymphocytes from healthy population. CONCLUSION: Despite the presence of BCL-2/IgH rearrangements, the accumulation of B lymphocytes in PPBL is not related to an overexpression of BCL-2 protein.

Adult↗

Chronic lymphocytic leukemia associated with myelodysplastic syndrome and/or chronic myeloid leukemia: evidence for independent clonal chromosomal evolution.

We describe the cytogenetic findings of three cases with simultaneous or sequential development of a B-chronic lymphocytic leukemia (B-CLL) and either a myelodysplastic syndrome (MDS) in 2 cases or a chronic myeloid leukemia (CML) in one case. The coexistence of these two hematologic malignancies leads to questions about their cell of origin. Through analysis of the cytogenetic abnormalities, we studied the derivation of both malignancies. The cytogenetic analyses of these three patients were simultaneously studied from both peripheral blood and bone marrow. Furthermore unstimulated short-time (USSTC) and long-time (72-96 hours) stimulated cultures (LTSC) were systematically performed. In all cases, we have demonstrated the independent bi-clonal evolution. This is the first report ever described for patients with CLPD and MDS and/or MPD shown to arise from distinct chromosomal abnormalities.

Aged↗

Defining the efficiency of fluorescence in situ hybridization on uncultured amniocytes on a retrospective cohort of 27407 prenatal diagnoses.

Rapid prenatal detection of selected numerical chromosomal abnormalities by using fluorescence in situ hybridization (FISH) on uncultured amniotic fluid samples was described six years ago. It allows a very rapid identification of selected aneuploidies. We have indexed the results of our 27407 fetal karyotypes obtained by conventional cytogenetics during the last five years, noting the type of chromosomal abnormality and the reasons for prenatal diagnosis. We have also indexed the chromosomal abnormality regarding the prognosis of the chromosomal aberations to evaluate the real impact of a non-diagnosis. Within the population of bad prognosis abnormalities, the percentage of abnormalities with bad prognosis detectable by FISH is 94.6% for advanced maternal age, 85.3% for ultrasonographic anomalies and 86.4% for positive maternal screening. The use of FISH alone on our cohort is not a suitable method to diagnose the chromosomal abnormalities.

Adult↗

Persistent polyclonal B lymphocytosis with binucleated lymphocytes: a study of 25 cases. Groupe Français d'Hématologie Cellulaire.

Persistent and polyclonal lymphocytosis of B lymphocytes (PPBL) with binucleated lymphocytes is an entity characterized by a polyclonal lymphocytosis. The lymphocytosis is stable for years and binucleated lymphocytes are detected on peripheral blood smears. We previously described +i(3q) as a recurrent chromosomal abnormality in seven PPBL patients. In this study we report a large series of 25 PPBL patients and demonstrated that PPBL was associated with +i(3q) in 77% of cases, premature chromosome condensation (PCC) in 50% and both abnormalities in 41% of cases. Furthermore, we demonstrated that i(3q) was present in a minority of B cells, restricted to B lymphocytes independently of the kappa or lambda light Ig chain expression, and exclusively observed in non-binucleated cells. The benign clinical course of PPBL and the lack of biological evolution in the majority of cases suggest that recognition of these disorders is so important that aggressive therapy in PPBL has to be avoided. Whether this syndrome represents a premalignant or benign disease remains unclear. The persistence of cytogenetic abnormalities after stopping tobacco use suggests no association with cigarette smoking.

Adult↗

[Polyclonal lymphocytosis with binucleated lymphocytes. Morphological, immunological, cytogenetic and molecular analysis in 15 cases].

OBJECTIVES: Describe the clinical, immunological, cytogenetic and molecular aspects of polyclonal lymphocytosis with binucleated peripheral lymphocytes in order to ascertain the therapeutic consequences. PATIENTS AND METHODS: Fifteen patients, 13 women, 2 men, with a total lymphocyte count persistently above 4 x 10(9)/l at successive counts and binucleated lymphocytes on blood smears were studied. RESULTS: The syndrome is easily recognized at careful examination of blood smears which show binucleated lymphocytes and lymphoid cells with heterogeneous morphology. The lymphocytosis is polyclonal. The clinical situation remains stable without treatment despite cytogenetic clonality which contrasts with molecular polyclonality. DISCUSSION: Polyclonal lymphocytosis with binucleated lymphocytes is a clinical entity characterized by 1) nearly exclusive female predominance, mainly in young smokers; 2) lymphocyte counts above 4 x 10(9)/l which persist (> 6 months), are unchanged over time and fortuitously discovered; 3) lymphocytosis with binucleated lymphocytes on blood smears; 4) polyclonal lymphocytosis; 5) increased polyclonal serum IgM; and 6) recurrent cytogenetic anomalies with an isochromosome supenumerary marker, e.g. +i (3q). The etiology remains unknown: the role of smoking genetic predisposition or viral factors remains to be determined.

Adult↗

The 17p-syndrome: a distinct myelodysplastic syndrome entity?

The 17p- syndrome is a subset of myelodysplastic syndrome characterized by "typical" dysgranulopoïesis, combining a pseudo-Pelger-Hüet and a deletion of the short arm of chromosome 17. We describe two patients; one with de novo myelodysplastic syndrome (RAEB), one with secondary MDS (RAEB-T). Both showed a 17p- deletion resulting from tanslocations involving 17p associated with an additional complex cytogenetics, and both of them had a particular type of dysgranulopoiesis, combining pseudo-Pelger-Hüet anomaly.

Aged↗

Chronic lymphocytic leukaemia with binucleated lymphocytes.

Chronic lymphocytic leukaemia (CLL) is a monoclonal proliferation usually involving B cells and composed of mature lymphoid cells. Distinct morphologic subtypes have been recognized according to lymphocyte size, nuclear:cytoplastic ratio and nucleolus. However the presence of characteristically binucleated lymphocytes in patients fulfilling criteria for CLL diagnosis has never been described. We here report immunological and cytogenetic studies of four patients with CLL but with binucleated lymphocytes. Moreover, trisomy 12, known to be associated with atypical morphology in CLL, was detected in two of these four patients. We suggest that this be considered as a possible new entity.

Aged↗

Isochromosome i(3q) and premature chromosome condensation are recurrent findings in chronic B-cell lymphocytosis with binucleated lymphocytes.

Chronic B lymphocytosis with binucleated lymphocytes (LWBL) is a recently described entity. The lymphocytosis is stable over years and atypical binucleated lymphocytes are detected on peripheral blood smears. Further investigation has shown a predominance in females, a polyclonal increase in serum IgM and HLA-DR7 expression in most cases. In almost all cases cytogenetic studies with classical culture conditions have not shown any abnormality. We describe 7 patients with LWBL associated with an abnormal karyotype. An additional i(3q) was found in 6 cases. Premature chromosome condensation (PCC) was detected in all 7 cases. As both abnormalities are rarely present in other benign or malignant proliferations, we suggest a strong correlation between LWBL and i(3q) and/or PCC.

Adult↗

Trisomy 8q due to i(8q) or der(8) t(8;8) is a frequent lesion in T-prolymphocytic leukaemia: four new cases and a review of the literature.

Cytogenetic abnormalities found in four cases of T-cell prolymphocytic leukaemia (T-PLL) are described. An isochromosome 8q was found in three patients and a t(8;8) in one. In the four cases, karyotypes were complex and showed a high degree of instability. In addition, we reviewed 27 published cases of cytogenetically studied T-PLL. On the whole, the most frequently recurring anomalies in T-PLL are 14q lesions with nonrandom breakpoints, inversion (14)(q11q32) or tandem translocations (14;14) (not seen in any of our cases) and trisomy for 8q. mainly due to i(8q), found in more than 40% of patients each. Similar structural anomalies were found almost as frequently among the 23 cytogenetically studied cases of so-called T-chronic lymphocytic leukaemia (T-CLL) reported prior to 1989. It is now accepted that the T-cell counterpart of B-CLL either does not exist or is exceedingly rare and thus previously reported cases of T-CLL sharing the chromosomal characteristics of T-PLL may well have been misdiagnosed examples of T-PLL. Isochromosomes 8q are exceptionally found in other types of haematological malignancies. However, i(8q) could not be shown to be the primary lesion in any case in T-PLL and the role of trisomy for 8q, as well of the associated monosomy 8p, is entirely unknown.

Adult↗

Use of various mitogens and cell stimulation index in 21 patients with chronic lymphocytic leukaemia.

A number of mitogens was used in 21 chronic B-lymphocytic leukaemia patients. Thymidine uptake assays were performed to evaluate cell stimulation. Phytohemagglutinin and phorbol-myristate 13 acetate were found to be the most efficient on cell proliferation. Abnormal clones were found 7 times with PMA, 4 times with PHA, twice with pokeweed, but in no case with lipopolysaccharide or proteine-A. The efficiency of PHA as a B-cell activator is likely to be due to T cell mediation.

Adult↗

Karyotypes of 33 patients with clonal aberrations in chronic lymphocytic leukaemia. Review of 216 abnormal karyotypes in chronic lymphocytic leukaemia.

We report on 33 unpublished patients with clonal anomalies in chronic lymphocytic leukaemia. The literature was thoroughly reviewed in order 1) to quantify the frequency of anomalies found in chronic lymphocytic leukaemia and to give new status to the rarest, 2) to determine whether a given anomaly was an additional anomaly and/or a primary anomaly, and 3) to find out whether strong associations between different anomalies exist in this disease.

Chromosome Aberrations↗

[Acute leukemia with translocation (8;16)].

Three cases of M5 acute leukemia, 1 with a t(8;16)(p11;p13), 2 with variant translocations, both with a breakpoint at band 8p11, t(6;8)(q27;p11) and t(8;19)(p11;q13) are reported and 12 other published cases reviewed. This is a rare new entity, of variable but rather poor prognosis, seen from birth to 75 years of age, with several cases in infants. Leukemic cells, which often show conspicuous phagocytic activity on bone marrow smears, bear both monocytic and granulocytic markers in at least some cases. The best therapeutic regimen is not well-defined. The molecular basis of the disorder remains to be elucidated.

Adult↗