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C Preudhomme

Publications and source records attributed to C Preudhomme.

At least 109 records · Page 6Linked to original sources
PubMed1993

De novo myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 20: a subtype of MDS with distinct hematological and prognostic features?

We report on 8 cases of de novo myelodysplastic syndromes (MDS) with deletion of the long arm of chromosome 20 (del 20q), who represented about 2% (8/392) of our cases of de novo MDS with cytogenetic analysis seen during a period of 9 yr. Median age was 69 yr, and there were 7 males and 1 female. Anemia was absent or very mild (Hb > 11 g/dl) in 5 patients. Only 1 patient had neutrophils < 0.5 x 10(9)/l, and none had platelets < 50 x 10(9)/l. Four patients had refractory anemia (RA), 2 had refractory anemia with ringed sideroblasts (RARS), and 2 had refractory anemia with excess of blasts (RAEB). Del 20q was isolated in 5 patients, and associated with other chromosomal rearrangement(s) in 3 patients. Only 1 patient progressed to ANLL and 2 showed an increase in bone marrow blasts during evolution. The 5 other patients had stable disease after 18-77 months. By comparison with de novo MDS patients with other cytogenetic findings, patients with del 20q had a tendency towards lower incidence of anemia and excess of marrow blasts, lower incidence of progression to AML and more prolonged survival, although differences were not significant. Only patients with isolated del 5q had a more prolonged survival than patients with del 20q.

Aged↗
PubMed1993

Absence of germline mutations of exons 5 to 8 of the P53 gene in 26 breast cancer families from the north of France.

We looked for germline mutations of exons 5 to 8 of the P53 gene in 27 female patients from 26 families originating from the north of France who had breast cancer and at least one first degree relative also affected with breast cancer. Detection of the mutations was made by single strand conformation polymorphism analysis. No mutation was found in any patient, confirming that germline mutations of the P53 gene are very rare in familial breast cancer (apart from Li Fraumeni families).

Adult↗
PubMed1993

Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients.

Cytogenetic analysis was successfully performed in 46 consecutive myeloma patients (40 newly diagnosed and six relapsed patients). Karyotype was performed on bone marrow cells after long-term cultures (6 d) stimulated by GM-CSF, GM-CSF+IL6 or GM-CSF+IL6+IL3. Nineteen patients (41%) had cytogenetic abnormalities including 17/40 patients at diagnosis (42.5%) and 2/6 patients at relapse. Hyperdiploidy was found in 12 patients and hypodiploidy in four patients. Of the 17 newly diagnosed patients with cytogenetic abnormalities, five died from myeloma after 1-14 months and three other patients had primary drug resistance. Our results suggest that cytogenetic analysis after stimulation of cultures by cytokines detects clonal abnormalities in 40-50% of newly diagnosed myeloma patients and that these patients often have a short survival and/or primary drug resistance.

Bone Marrow↗
PubMed1993

Immunological detection of myeloperoxidase in poorly differentiated acute leukemia.

We performed immunocytochemical detection of myeloperoxidase (MPO), using monoclonal antibody MPO-7, in 15 consecutive cases of adult acute leukemia (AL) unclassified by conventional cytological and cytochemical criteria and 7 AML-M1 with less than 10% of cytochemically MPO-positive blasts. In AL with negative MPO cytochemistry the anti-MPO reaction was positive in 5 of the 15 patients with 3, 3, 7, 11 and 45% positive blasts respectively. In AML-M1, immunocytochemistry was positive in a larger percentage of blasts than cytochemistry in 2 cases. Immunological detection of myeloid surface markers was positive in all 15 cases of unclassified AL (including the 10 AL with negative anti-MPO reaction). Eleven of the 22 patients from this study had mixed lymphoid-myeloid phenotype. Discrepancy between immunological MPO detection and light cytochemistry was more frequent in patients with mixed immunophenotype than in patients without lymphoid markers. No relationship between MPO-antigen positivity and clinical or biological features was seen. These findings confirm immunological detection of MPO as useful for the diagnosis of poorly differentiated AL. The high incidence of inactive MPO detectable only by immunocytochemistry in mixed lineage AL needs to be confirmed.

Acute Disease↗
PubMed1993

Relationship between p53 gene mutations and multidrug resistance (mdr1) gene expression in myelodysplastic syndromes.

P glycoprotein, the product of multidrug resistance (mdr1) gene, is frequently expressed in advanced myelodysplastic syndromes (MDS) with an excess of bone marrow blasts and could explain their frequent resistance to chemotherapy. P53 gene mutations are also found in 10 to 15% of advanced MDS. Because it has recently been suggested that normal p53 suppressed, but that mutated p53 activated, the mdr1 gene promoter, we tried to correlate p53 mutations and P glycoprotein expression in 34 patients with MDS and an excess of bone marrow blasts (> 5%). P glycoprotein expression was assessed by immunocytochemistry using JSB1 monoclonal antibody and was found positive in 13 out of the 34 patients. p53 mutations were detected both by immunocytochemistry using three different monoclonal antibodies and by single stranded conformation polymorphism (SSCP) analysis of exons 5 to 8 of the P53 gene. Both methods detected a point mutation in 5 out of the 34 patients. Only one out of the 5 patients with a p53 mutation expressed P glycoprotein, as compared to 12 out of the 29 patients without p53 mutations. This suggested the mutant and normal p53 are not major determinants of the regulation of mdr1 expression in vivo, at least in MDS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Philadelphia negative, BCR-ABL positive adult acute lymphoblastic leukemia (ALL) in 2 of 39 patients with combined cytogenetic and molecular analysis.

We performed cytogenetic and molecular analysis of the BCR-ABL rearrangement by polymerase chain reaction (PCR) in 39 consecutive cases of adult acute lymphoblastic leukemia (ALL). Eleven patients had a Philadelphia (Ph) chromosome. Thirteen patients had a BCR-ABL rearrangement, involving minor breakpoint cluster region (m-bcr, situated in intron 1 of the BCR gene) in 11 cases, and major breakpoint cluster region (M-bcr, 'specific' of chronic myeloid leukemia) in the remaining two cases. All of the 12 BCR-ABL cases studied immunologically were of early B, CALLA-positive immunophenotype. The 13 BCR-ABL positive cases included the 11 Ph-positive cases, and two patients with normal karyotype at diagnosis. In the two Ph-negative BCR-positive cases, seven (patient 1) and 18 (patient 2) mitoses had been examined at diagnosis. In patient 1, Ph negativity at diagnosis could certainly be explained by the small number of mitoses analyzed, as a Ph chromosome was found at relapse. This was less probable in patient 2, who raised the issue of whether authentic Ph-negative BCR-ABL-positive ALL exists (as in the chronic myeloid leukemia model) or not. Whatever the explanation, our results suggest that molecular detection of BCR-ABL should be more widely used in B-lineage ALL.

Adult↗
PubMed1993

Absence of amplification of MDM2 gene, a regulator of p53 function, in myelodysplastic syndromes.

The MDM2 gene is a gene whose product binds to p53 and regulates its function. Amplification of MDM2 has been found in human sarcomas, where it leads to inactivation of p53. In 64 cases of generally advanced myelodysplastic syndromes, we found no amplification or rearrangement of MDM2 gene by Southern analysis. MDM2 RNA was also normal in the 15 cases where Northern analysis was made. Thus, amplification of MDM2 is not seen or must be very rare in myelodysplastic syndrome (MDS). Because P53 gene mutations are not frequent in MDS, inactivation of p53 seems to be, overall, a rare pathogenetic event in MDS.

Blotting, Southern↗
PubMed1993

Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases.

Although the prognostic value of cytogenetic analysis has previously been demonstrated in myelodysplastic syndromes (MDS), karyotype had not been included in previously published scoring systems, such as Bournemouth and Sanz's scores. We studied karyotype at diagnosis in 408 cases of de novo MDS (after excluding therapy-related MDS). Karyotypes were classified in 10 groups: normal; isolated del 5q; del 5q and other rearrangements; isolated +8; isolated -7 or del 7q; del 20q; isolated -Y; miscellaneous single rearrangements; -7 or del 7q and other rearrangements; miscellaneous complex rearrangements. Karyotypes were considered complex when at least three chromosomes were rearranged. Complex karyotypes included all patients with del 5q and other rearrangements, -7 or del 7q and other rearrangements, and miscellaneous complex rearrangements (i.e. three of the 10 groups). Median actuarial survival of the 408 patients was 28 months, and 90 patients (22%) progressed to acute myeloid leukemia (AML). For survival, bone marrow (BM) blasts, circulating blasts, white blood cell (WBC), neutrophil count, platelet count, hemoglobin, age, sex, FAB classification, and Bournemouth and Sanz's scores had strong prognostic value. Cytogenetics also had strong prognostic value. An unfavorable cytogenetic group (patients with complex karyotypes) was identified. On the other hand, although patients with isolated del 20q and del 5q had a somewhat better prognosis than other patients with non-complex cytogenetic findings, they could not be statistically individualized as a favorable group, possibly owing to their relatively limited number. By multivariate regression analysis, a three-variable new scoring system could be designed based on karyotype (1 point for complex karyotype; 0 for other groups), platelets (0 for > 75 x 10(9)/l; 1 for < 75 x 10(9)/l), and BM blasts (0 for < 5%, 1 for 5-10%, 2 for > 10%). The total score (addition of points for the three variables) was able to separate patients in three groups with low (score 0) intermediate (score 1 or 2), and high risk (score 3 or 4) which included 34%, 47%, and 19% of the patients, and had a median survival of 55, 24, and 6 months, respectively (chi 2 = 110, p < 10(-4)). This new score (Lille score) was able to subdivide risk groups according to Bournemouth and Sanz's scores into further subgroups of different prognoses. For progression to AML, BM blasts, circulating blasts, WBC count, hemoglobin, FAB type, and karyotype had prognostic value by univariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13).

A new case of acute monocytic leukemia observed in a 73-year-old male (ANLLM5) with an unusual t(8;22)(p11;q13) is reported. The blasts did not demonstrate erythrophagocytosis, but the presence of both naphthol-ASD-chloro-acetate esterase and butyrate esterase activities was similar to that seen in cases with t(8;16)(p11;p13). Involvement of the 8p11 region in ANLLM4 and M5 is discussed, being the third most frequent rearrangement in acute leukemia with monocytic components seen at our Center.

Aged↗
PubMed1992

Rare occurrence of P53 gene mutations in multiple myeloma.

We looked for mutations of exons 5-8 of the P53 gene in bone marrow cell from 37 cases of multiple myeloma, using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. 25 patients also had cytogenetic analysis. A point mutation, leading to an amino acid change in the P53 protein was found in only one case, involving exon 5. These findings suggest that P53 mutations are very rare in multiple myeloma, and that this disease may be categorized among the few neoplasms where P53 abnormalities have very limited role, if any.

Base Sequence↗
PubMed1992

Mutations of the P53 gene in acute myeloid leukaemia.

In a previous report we found point mutations in exons 5-8 of the P53 gene in five of 46 patients with acute myeloid leukaemia (AML), with a predominance of mutations in the 10 patients with 17p monosomy. In this report we extended our findings studying such mutations in 66 unselected additional cases of AML, using polymerase chain reaction single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing. Three of the 66 new cases had a point mutation, leading to a change in one encoded amino acid. Thus, eight of the 112 AML studied had P53 mutations in exons 5-8, suggesting that the incidence of P53 mutation is relatively low in AML. A predominance of mutations in exon 8 (5/8) was found. Six of the eight patients with mutations were older than 60 years of age, and all eight cases had a short survival. All seven mutated cases karyotyped showed complex cytogenetic findings, especially monosomy 5 and/or 7, thus questioning the pathogenic importance of P53 mutations in a context of multiple genetic abnormalities. However, five of them also had 17p monosomy, and in the remaining two cases SSCP and sequence analysis also suggested loss of the normal P53 allele. This supported a role for the P53 gene mutations in leukaemogenesis in the relatively small number of AML patients in whom they were found, through loss of tumour suppressive activity of both normal P53 alleles, as reported in solid tumours.

Acute Disease↗
PubMed1992

The role of intensive chemotherapy in myelodysplastic syndromes.

We review results of intensive chemotherapy (IC) obtained in myelodysplastic syndromes (MDS). Overall, the complete remission (CR) rates and median CR duration obtained with IC are low in MDS, especially when compared to results obtained in de novo AML treated with the same chemotherapy regimens; very few MDS patients achieve prolonged remissions. Failure to achieve CR, in MDS, results both from a high incidence of resistant disease and toxic deaths, the latter being due to longer periods of aplasia than in de novo AML. However some subgroups of MDS seem to obtain higher CR rates and more prolonged remissions. These include patients younger than 45 to 50 years, those with a large excess of marrow blasts or Auer rods at diagnosis, and patients with a normal karyotype or at least without involvement of chromosomes 5 and/or 7. Results of IC clearly have to be improved in MDS. Higher CR rates may possibly be obtained by intensifying induction regimens, but this will probably require the addition of growth factors, in order to reduce the already very long periods of aplasia seen with IC in MDS. For consolidation therapy, new approaches, and especially autologous bone marrow transplantation, will have to be investigated.

Adult↗
PubMed1992

Mutations of the p53 gene in B-cell chronic lymphocytic leukemia: a report on 39 cases with cytogenetic analysis.

Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia (CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing. All patients also had cytogenetic analysis. A point mutation, leading to an amino acid change in the p53 protein was found in four cases, involving exon 7 (one case) or exon 8 (three cases). Mutations seemed to predominate in advanced clinical stages (Binet's stage C). All four patients with 17p monosomy had a mutation whereas no mutation was found in the 35 patients with cytogenetically normal 17p. These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series). In those patients, the mutations may play a role in leukemogenesis through loss of tumor suppressive activity of normal p53 genes.

Aged↗
PubMed1992

Mutations of the p53 gene in B-cell lymphoblastic acute leukemia: a report on 60 cases.

Exons 5 to 8 of the p53 gene were examined for mutations in 60 patients with B-cell acute lymphoblastic leukemia (ALL), including 50 cases of precursor-B-cell ALL, nine cases of Burkitt (L3) ALL and one case of atypical ALL with surface immunoglobulins and t(8:14) translocation but L2 morphology. Karyotype was available in all patients. DNA was analyzed by polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Three patients showed point mutations in exons 7 or 8, including two of the nine patients with Burkitt ALL and one of the 50 patients with precursor-B-cell ALL. These findings suggest that p53 gene mutations are rare in precursor-B-cell ALL but may be more frequent in Burkitt ALL. In the three patients with p53 mutations, however, the relevance of those mutations to the development or progression of leukemia remained uncertain.

Amino Acid Sequence↗
PubMed1990

de novo myelodysplastic syndromes in adults aged 50 or less. A report on 37 cases.

We report on 37 adults aged 50 years or less with de novo myelodysplastic syndrome (MDS) (excluding cases secondary to chemo or radiotherapy), who represented 6.7% of our total cases of adult MDS. Median age was 42 (range 18-50). At diagnosis, there were 9 RA, 6 RAEB, 13 RAEB-T, 9 CMML but no RARS. Five patients had a familial history of MDS, and 3 a history of occupational exposure to potential carcinogens. Twenty-one patients received intensive chemotherapy (at diagnosis or during the evolution) but only 8 (38%) achieved complete remission (CR), and median CR duration was 10 months. Five patients were allografted (3 of them as first line therapy): 2 remained disease free after 12 and 10 months, and 3 died of transplant related complications. Median actuarial survival of the 37 patients was 21 months. Significantly shorter survival was seen in patients who had circulating blasts, Bournemouth score greater than 1 or 2, abnormal karyotype (especially monosomy 7) and RAEB or CMML. When compared with our MDS aged more than 50, our MDS aged 50 or less were characterized by more familial cases, more cases of RAEB-T and less cases of RAEB and RARS, more frequent abnormal karyotype and monosomy 7, more frequent progression to AML, identical overall survival but longer survival in RAEB-T and shorter survival in CMML. MDS in younger adults seem relatively often familiar or associated to occupational exposure. They have a poor prognosis with conventional therapeutic approaches and therefore require allografting, whenever possible.

Actuarial Analysis↗
PubMed1990

Prognostic value of dysmyelopoietic features in de novo acute myeloid leukaemia: a report on 132 patients.

The prognostic value of cytological features was assessed in 132 patients with de novo acute myeloid leukaemia (AML) treated by anthracycline-cytosine-arabinoside combination chemotherapy. Of these patients, 98 (75%) achieved complete remission (CR). A significantly lower CR rate was seen in patients with trilineage dysmyelopoiesis (TDMP) (P = 0.003), but not in patients with dyserythropoiesis and/or dysgranulopoiesis without abnormal megakaryocytes. Other unfavourable factors were age greater than 50 years (P = 0.042), leucocyte count greater than 100 x 10(9)/l (P = 0.006), M5 FAB subtype (P = 0.013), presence of complex cytogenetic rearrangement or abnormalities of chromosome 5 and/or 7 (P = 0.001). Bone marrow eosinophilia greater than 3% was significantly associated with a higher CR rate (P = 0.04). In a multivariate analysis, a low CR rate was best predicted by the presence of a complex karyotype or abnormalities of chromosome 5 and/or 7 (P = 0.0001) and by the TDMP (P = 0.0036). Median actuarial disease-free survival (DFS) was 24 months. Actuarial DFS was significantly shorter in patients with TDMP (P = 0.0001) and an elevated leucocyte count (P = 0.02). Age, FAB subtype and karyotype had no significant incidence on DFS. Presence of TDMP appears to be an important prognostic factor in de novo AML. This could be used as one of the guidelines to therapy.

Adolescent↗