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A Cantù-Rajnoldi

Publications and source records attributed to A Cantù-Rajnoldi.

At least 19 recordsLinked to original sources
PubMed2000

A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements.

Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of the PML/RARA fusion gene and predicts a beneficial response to retinoids. However, approximately 10% of all APL cases lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA gene rearrangements and t(5;17) that leads to the NPM/RARA fusion gene, which are retinoid-responsive, and (2) cases with t(11;17)(q23;q21) that are associated with the PLZF/RARA fusion gene, which are retinoid-resistant. A key issue is how to rapidly distinguish subtypes of APL that demand distinct treatment approaches. To address this issue, a European workshop was held in Monza, Italy, during June 1997, and a morphologic, immunophenotypic, cytogenetic, and molecular review was undertaken in 60 cases of APL lacking t(15;17). This process led to the development of a novel morphologic classification system that takes into account the major nuclear and cytoplasmic features of APL. There were no major differences observed in morphology or immunophenotype between cases with the classic t(15;17) and those with the cryptic PML/RARA gene rearrangements. Auer rods were absent in the t(5;17) case expressing NPM/RARA. Interestingly, this classification system distinguished 9 cases with t(11;17)(q23;q21) and, in addition, successfully identified 2 cases lacking t(11;17), which were subsequently shown to have underlying PLZF/RARA fusions. The PLZF/RARA cases were characterized by a predominance of blasts with regular nuclei, an increased number of Pelger-like cells, and by expression of CD56 in 4 of 6 cases tested. Use of this classification system, combined with an analysis for CD56 expression, should allow early recognition of APL cases requiring tailored molecular investigations. (Blood. 2000;96:1287-1296)

DNA-Binding Proteins↗
PubMed1998

Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases.

Acute promyelocytic leukaemia (APL), characterized by a specific PML-RARalpha fusion gene resulting from translocation t(15;17) and by a high response rate to differentiation therapy with all-trans retinoic acid, presents clinical (varying WBC counts, age and treatment outcome), morphological (hypergranular M3 and hypogranular M3V) and molecular (three isoforms of PML breakpoint) heterogeneity. We correlated leukaemic immunophenotype with these aspects in 196 molecularly confirmed APLs (63 children and 133 adults) in Italy. The bcr3 isoform (P = 0.05) and FAB M3V (P = 0.05) were more frequent in children. We confirmed in APL an immunophenotype characterized by frequent expression of CD13, CD33 and CD9 and rare expression of HLA-DR, CD10, CD7 and CD11b. However, we recognized CD2 in 28%, CD34 in 23% and CD19 in 11% of cases and demonstrated by double labelling that CD34 and CD2 may be co-expressed. CD2, CD34 and CD19 were significantly intercorrelated, and variably associated to other features: CD2 and CD34 with PML bcr3 (P < 0.001 and P < 0.001, respectively) and with M3V (P < 0.001 and P = 0.002), whereas only CD19 was directly correlated with WBC counts and only CD2 positively influenced CR rate (logistic model) and event-free survival (Cox model). We conclude that immunophenotype plays a role in the determination of the biological and clinical heterogeneity of childhood and adult APL.

Adolescent↗
PubMed1998

Clinical relevance of CD10 expression in childhood ALL. The Italian Association for Pediatric Hematology and Oncology (AIEOP).

BACKGROUND AND OBJECTIVE: Previous studies have considered the prognostic significance of CD10 expression in childhood acute lymphoblastic leukemia (ALL) and showed its linkage to a more favorable prognosis. The aim of this study was to assess the independent significance of CD10 expression in a large population of ALL patients. DESIGN AND METHODS: We revised the independent clinical relevance of CD10 expression in 2038 children with acute lymphoblastic leukemia (ALL), who were consecutively entered in 4 sequential trials of the Italian Association for Pediatric Hematology and Oncology (i.e. AIEOP studies 82, 87, 88, 91); 1142 were males and 896 females, age ranged between 1 and 14 years (yrs) at diagnosis. Of the whole group, 1471 children (72.2%) were defined as having standard risk, 567 (27.8%) as having a high risk. RESULTS: CD10 was detected in blast cells from 1706 of 1784 (95.6%) patients with B-lineage ALL and 46 of 254 (18.1%) with T-cell ALL. In the B-lineage subgroup CD10 expression was associated with presenting features such as age < 9 yrs and inclusion in the standard risk category. No significant differences were found between CD10+ and CD10- cases in T-lineage ALL, concerning presenting features, except for FAB L2 in the former group. We compared the event-free survival (EFS) rates for patients with T-ALL or B-lineage ALL, regarding CD10 positivity, overall and by individual study. Patients with T-ALL fared worse than those with B-lineage ALL (5 and 10 yrs EFS: 46.8% vs. 68.5% and 44.5% vs. 63.7% respectively, p = 0.0001). In multivariate analysis of B-lineage subgroup poorer EFS was associated with male sex, higher WBC (> or = 20 x 10(9)/L), age > 9 yrs. Only WBC > or = 20 x 10(9)/L and age > 9 yrs were parameters linked to poorer EFS in the T-lineage subgroup. Finally, we compared EFS rates for four groups of patients categorized as having high or standard risk, and according to CD10+ and CD10- expression. High-risk patients fared statistically worse than standard risk patients both in the CD10- and in the CD10+ groups (42% vs. 50.7% and 63.6% vs. 66.8%, respectively). INTERPRETATION AND CONCLUSIONS: CD10 expression does not have independent prognostic significance in either the larger subgroup of B-ALL patients or in T-cell ALL.

Adolescent↗
PubMed1997

A severe transfusion-dependent congenital dyserythropoietic anaemia presenting as hydrops fetalis.

We describe a case of congenital dyserythropoietic anaemia (CDA) presenting at week 20 of pregnancy with hydrops fetalis and very severe anaemia. Fetal blood examination showed marked erythroblastosis with morphologic alterations while the basic haematological and biochemical tests were in the normal range. The fetus received intravascular red blood cells transfusion at 20 and 25 weeks of gestation. After a caesarean section at week 33 the child became transfusion dependent. Haematological investigations demonstrated that the child is affected by a CDA-like picture which, although morphologically similar to CDA II, is Ham test negative and does not show the typical membrane proteins alterations.

Adult↗
PubMed1995

CD2 expression in acute promyelocytic leukemia is associated with microgranular morphology (FAB M3v) but not with any PML gene breakpoint.

In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.

Adolescent↗
PubMed1994

Acute promyelocytic leukemia in children: experience of the Italian Pediatric Hematology and Oncology Group (AIEOP).

Scanty information is available on acute promyelocytic leukemia (APL) in children, and whether differences are present with respect to the adult form. The experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be presented with respect to the following aspects: 1. Incidence of APL. The incidence of APL is generally considered to account for 3-9% of acute myelogenous leukemia (AML) in children and approximately 10-15% in adults. Recently a single Italian pediatric institution reported that APL constituted one third of observed acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study group have confirmed that APL in Italy is more frequently observed in children as compared to other countries. Environmental and/or genetic factors should be considered to explain such differences. 2. Diagnosis of M3v. The clinical and biological features of the largest series of childhood M3v will be presented and the problems encountered in the proper separation of 'classic' M3 and M3v in children will be discussed. 3. Clinical Aspects. The clinical features of the APL patients enrolled in the AIEOP study groups since 1989, will be presented with emphasis on the recent experience with the use of all-trans retinoic acid. 4. Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric APL cases from cryopreserved bone marrow samples has been performed. It is concluded that APL in children did not differ significantly from the adult form, with the exception of a higher incidence of PML bcr3 breakpoint.

Age Factors↗
PubMed1994

Acute promyelocytic leukemia in children: experience of the Italian Pediatric Hematology and Oncology Group (AIEOP).

Scanty information is available on acute promyelocytic leukemia (APL) in children, and whether differences are present with respect to the adult form. The experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be presented with respect to the following aspects: 1. Incidence of APL. The incidence of APL is generally considered to account for 3-9% of acute myelogenous leukemia (AML) in children and approximately 10-15% in adults. Recently a single Italian pediatric institution reported that APL constituted one third of observed acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study group have confirmed that APL in Italy is more frequently observed in children as compared to other countries. Environmental and/or genetic factors should be considered to explain such differences. 2. Diagnosis of M3v. The clinical and biological features of the largest series of childhood M3v will be presented and the problems encountered in the proper separation of 'classic' M3 and M3v in children will be discussed. 3. Clinical Aspects. The clinical features of the APL patients enrolled in the AIEOP study groups since 1989, will be presented with emphasis on the recent experience with the use of all-trans retinoic acid. 4. Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric APL cases from cryopreserved bone marrow samples has been performed. It is concluded that APL in children did not differ significantly from the adult form, with the exception of a higher incidence of PML bcr3 breakpoint.

Adolescent↗
PubMed1992

Extravillus dividing fetal cells at CVS: evidence of their erythroblastic origin.

Cytological and cytogenetic studies were performed on nucleated fetal cells present in chorionic villus transport medium. The erythroblastic origin of these cells was shown. Fetal erythroblasts in spontaneous mitosis were frequently observed; chromosome counts were obtained from them but poor quality often prevented banded analysis. Cytogenetic study of erythroblast metaphases can be useful as an additional diagnostic aid in cases of mosaicism with aneuploid cell lines.

Amniotic Fluid↗
PubMed1992

An unclassified case of congenital dyserythropoietic anaemia with a severe neonatal onset.

The case of a 13-year-old child with a congenital dyserythropoietic anaemia (CDA) is reported. A severe anaemia associated with a slight increase in reticulocytes, erythroblastosis, hyperbilirubinaemia, hepatosplenomegaly, generalized oedema and hypoproteinaemia was present at birth. Three exsanguino-transfusions were needed in the first 4 days of life. In the following years a continuous transfusional regimen was maintained in association with a chelating treatment. Bone marrow aspirates showed a striking hyperplasia of the erythroid lineage with ineffective erythropoiesis and changes of erythroblastic nuclei which were double but incompletely separated. Numerous histio-erythroblastic islands were also present. Electron microscopy studies did not show specific alterations of the erythropoietic cells. By a long-term evaluation of the clinical signs and of the haematological data, we came to the conclusion that the case does not fit into any of the three classical categories of CDA.

Adolescent↗
PubMed1992

Nonradioactive quantification of low concentrations of hemoglobin A by HPLC for midtrimester prenatal diagnosis of beta-thalassemia.

The usual methods for prenatal diagnosis of beta-thalassemia and other hemoglobinopathies by assay of fetal blood erythrocytes are either complex (analysis of globin chains synthesis by carboxymethylcellulose chromatography) or only semiquantitative [isoelectric focusing of hemoglobin (Hb)]. To further simplify the diagnostic procedure and to obtain quantitative data, we measured the small concentrations of Hb A in fetal erythrocytes by using a high-pressure liquid chromatography (HPLC) instrument (DIAMAT-TM; Bio-Rad) equipped with the new column proposed for measuring Hb A2. We analyzed 212 uncontaminated fetal blood samples obtained by cordocentesis between the 18th and 22nd weeks of pregnancy, using the HPLC procedure, and compared the results with those obtained by the above-named methods. The Hb A values obtained ranged between 0% and 8.5%; they were less than or equal to 1.8% in 44 fetuses affected by homozygous beta-thalassemia and greater than 2.5% in 168 unaffected fetuses. The method was simple, rapid, and reproducible (CV 3.2%) and there was good correlation between Hb A concentrations determined by HPLC and the beta/gamma ratio determined by carboxymethylcellulose chromatography (r = 0.7687; P less than 0.0001). No false-negative or false-positive results were observed, and there was no overlap of values between affected and unaffected fetuses.

Chromatography, High Pressure Liquid↗
PubMed1991

Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype.

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.

Acute Disease↗
PubMed1991

Co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia: relationship with the stage of differentiation and clinical significance.

Co-expression of myeloid antigens on the leukaemic blast cells was evaluated in 532 children with a diagnosis of acute lymphoblastic leukaemia (ALL). Using a panel of monoclonal antibodies belonging to CD11b, CD13, CD14, CD15 and CD33 an overall incidence of 4.3% was found, with values ranging between 1.8% for CD14 and 6.1% for CD15. When the data were further dissected, a significantly higher incidence of co-expression was noted in null-ALL (15/70 cases = 21.4%), compared to cases expressing a more mature immunophenotype, i.e. common-ALL (7/394 cases = 1.7%) and T-ALL (1/68 cases = 1.4%) (P less than 0.001). In null-ALL, 9/15 patients were infants, five of whom with the t(4;11); two further children also had a t(4;11). The clinical outcome of the 23 cases which co-expressed myeloid antigens was unfavourable. Only two of the 15 null-ALL, two of the seven common-ALL and the unique case with T-ALL are in fact in persistent first remission between 19 and 93 months from diagnosis. Though the overall incidence of childhood ALL expressing myeloid antigens is low, the evidence that this co-expression may be related to an unfavourable clinical course and that it more frequently occurs in null-ALL, particularly in the first year of life, suggests that the routine assessment of myeloid antigens may allow to identify a subgroup of childhood ALL with a poor clinical outcome.

Adolescent↗
PubMed1989

Biological and clinical features of acute lymphoblastic leukaemia with cytoplasmic granules or inclusions: description of eight cases.

We describe eight patients (four children and four adults) with an acute lymphoblastic leukaemia (ALL) with cytoplasmic granules or inclusions. The incidence of this variant of acute leukaemia in our whole series of patients with ALL is 1.8%. The granules or inclusions were usually positive for aspecific esterases (ANAE) and/or acid phosphatase, and the immunophenotype was in all cases typical of a CALLA positive B-lineage ALL (CD10+, CD19+ and/or CD24+, DR+, TdT+, anti-T-, anti-My-, SIg-). In one paediatric case, CD33 was unusually coexpressed. Ultrastructural investigations were performed in one case and demonstrated large granules containing vesicles, usually membrane bound, in the majority of blast cells. In the two cases analysed, Ig heavy chain gene rearrangement was detected. In this series of patients prognosis was poor since three never achieved a complete remission, four relapsed and only one is still in first continuous remission.

Acid Phosphatase↗
PubMed1989

T-cell receptor delta gene rearrangement in childhood T-cell acute lymphoblastic leukemia.

During the development of functional T lymphocytes, a variety of genes involved in antigen recognition undergo somatic rearrangement. These include the alpha, beta, and gamma chain genes. Recently a fourth rearranging gene, the delta chain gene, embedded in the alpha chain locus, has been described. We have determined the structure of the beta, gamma, and delta chain genes in 15 cases of T-cell acute lymphoblastic leukemia (T-ALL) representing stage I (CD7+, CD1-, CD3-) and stage II (CD7+, CD1+, CD3-) of intrathymic T-cell development. The alpha-delta locus was rearranged in 14 of the 15 cases. In three cases the delta constant region was deleted on both chromosomes, suggesting biallelic V-J alpha rearrangement. A limited pattern of rearrangement of the delta locus was observed in the remaining 11 cases. When the alpha-delta region was rearranged, there was rearrangement of the beta and gamma TcR in all cases except two; in these cases the beta chain was in the germline configuration. These findings support the hypothesis that delta chain gene rearrangement is an early event in T-cell development, possibly contemporary to gamma gene rearrangement, and that the delta locus has a limited repertoire.

Gene Rearrangement, T-Lymphocyte↗