PubMed Health⌕ Search

Biomedical subjects

A Zaccaria

Publications and source records attributed to A Zaccaria.

At least 91 records · Page 5Linked to original sources
PubMed1990

ABL proteins in Philadelphia-positive acute leukaemias and chronic myelogenous leukaemia blast crises.

The Philadelphia chromosome (Ph1) is present in 95% of chronic myelogenous leukaemias (CML) and 15% of acute lymphoblastic leukaemias (ALL). This cytogenetic marker is due to a t(9;22) translocation, which causes a rearrangement of the ABL oncogene. In order to better define the relationship between type of genomic rearrangement, variant ABL protein expressed and haematological phenotype, a series of Ph1-positive acute leukaemias, both myeloblastic (AML) and lymphoblastic, and several CML lymphoid blast crises have been analysed at the DNA and protein level. The results confirm the presence of the ABL protein P210 in all cases of CML, ALL and AML positive for rearrangement in the bcr region of chromosome 22, and, surprisingly, in one AML case apparently negative for bcr rearrangement. The ABL protein P190 was found to be present only in cases of ALL negative for bcr rearrangement. Polymerase chain reaction (PCR) analysis of the types of 9/22 junctions present in the mRNA of CML lymphoid blast crises showed no evidence of 'ALL-type' transcripts.

Adult↗
PubMed1989

Cytogenetic and molecular studies in patients with chronic myeloid leukemia and variant Philadelphia translocations.

Out of 105 Philadelphia (Ph) positive chronic myeloid leukemia patients analyzed, six (5.7%) carried a variant Ph translocation, namely t(6;9;9;10;22)(q24;p13;q34;p15;q11); t(9;13;22)(q34;q21;q11);der(2)(2pter----2q31::9q21---- 9q34::22q11----22qter) and der(9)t(2;9) (9pter----9q21::2q31----2qter);t(7;9;22)(q11;q34 ;q11), 14q + ;t(7;9;22)(q35;q34;q11), and t(9;11;22) (q34;q13;q11), respectively. Five of these patients were analyzed with Southern blotting. Three of them showed an atypical molecular pattern; namely, the patient with t(9;13;22) showed no rearrangement in the breakpoint cluster region (bcr), the patient with t(7;9;22)(q35;q34;q11) showed a 3' deletion, and the patient with t(7;9;22), 14q + showed a bcr rearrangement 3' to the exon 4 of the M-BCR. Chromosome in situ hybridization studies demonstrated that in patient one, a two-step translocation occurred: the first step moved the 3' bcr from chromosome 22 to chromosome 9, and the second moved the terminal part of 22q, carrying the c-sis protooncogene, to 10p. Variant Ph translocations appear to be associated with atypical molecular breakpoints.

Chromosome Banding↗
PubMed1989

Evaluation of complete remission in hairy cell leukemia patients treated with alpha-IFN.

In 10 HCL patients, who following treatment for more than 1 year with alpha-IFN, had achieved a normalization of the splenomegaly and a disappearance of circulating hairy cells together with a complete restoration of all peripheral hematological values, a multiple assessment of the apparent complete remission (CR) was carried out. The presence of residual disease was investigated by bone marrow histology, bone marrow immunohistochemistry, immunoglobulin (Ig) gene analysis and on the basis of the serum levels of the soluble form of the Interleukin-2 receptor (sIL-2R). Examination of bone marrow biopsies showed a pattern of CR in 5 cases; 4 of them revealed no evidence of Ig heavy chain gene rearrangement, as well as a near normalization of the serum levels of sIL-2R. Immunohistochemical studies were carried out on embedded paraffin sections with the monoclonal antibody 4KB5 (CD45R) and were assessable in 4 of the 5 patients considered in CR and in 3 of the 4 cases with no Ig gene rearrangement. In 2 the pattern of CR was confirmed, while in the 3rd a minimal but persistent disease (5%) was suspected.

Adult↗
PubMed1988

Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.

One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.

Adolescent↗
PubMed1988

Variability of the molecular defects corresponding to the presence of a Philadelphia chromosome in human hematologic malignancies.

By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and blast crisis) or lymphoid and myeloid Philadelphia chromosome (Ph') positive acute leukemias, we have investigated the relationship between the molecular defect on the Ph' chromosome and the associated hematologic phenotype. As expected, approximately half of the Ph' positive acute leukemias showed a breakpoint on chromosome 22 falling outside the "breakpoint cluster region" (bcr) known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic phase also showed rearrangements falling outside the bcr region. In two of these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb upstream to the bcr region. In another case, the breakpoint was located approximately 16 kb downstream to bcr. In the remaining four cases, the precise position of the rearrangement could not be localized with the available bcr probes. DNAs from patients with CML blast crises showed classical bcr rearrangements. No molecular changes were observed during the progression of the disease in six patients whose DNA from both a chronic and acute phase was available. Our results seem to indicate a greater degree of variability of chromosome 22 breakpoints in CML than previously observed, and the lack of additional rearrangements on the Ph' chromosome in CML blast crises with respect to chronic phase.

Adult↗
PubMed1987

Chromosome studies in patients with Philadelphia chromosome-positive chronic myeloid leukemia submitted to bone marrow transplantation--results of a European Cooperative Study.

The karyotypes of 74 patients with Ph-positive chronic myeloid leukemia submitted to bone marrow transplantation collected from nine institutions were studied serially before and after transplantation. In 13 cases sporadic Ph-positive metaphases were detected without signs of relapsing disease at various intervals after transplantation. These data indicate that the leukemic clone may not be completely suppressed by the conditioning treatment and that other biological mechanisms may be involved in destroying this clone or controlling its expansion.

Adolescent↗
PubMed1987

Chromosome studies in patients with acute nonlymphocytic or acute lymphocytic leukemia submitted to bone marrow transplantation--results of a European cooperative study.

The chromosomal data of 58 acute nonlymphocytic leukemia (ANLL) patients and of 32 acute lymphocytic leukemia (ALL) patients submitted to bone marrow transplantation and collected from nine institutions are reported. Chromosomal studies were available at diagnosis in 19 cases with ANLL: seven had a partially or completely abnormal pattern. Forty-one patients had a chromosome study before bone marrow transplantation and all had a normal pattern. Thirteen patients with ALL were studied at diagnosis: five had a partially or completely abnormal karyotype. Of 20 cases analyzed before bone marrow transplantation, only one has maintained the abnormal pattern of diagnosis in part of the cells. Karyotypes were available in nine ANLL patients relapsed after bone marrow transplantations. Two showed the same clonal abnormalities seen at diagnosis; in three other cases the leukemic clone of relapse carried an additional chromosome abnormality with respect to the pattern at diagnosis and four more cases presented at relapse complex abnormalities; two of them had a cytogenetically normal pattern at diagnosis. In four of ten relapsed ALL cases chromosomes analyses were available. A relapse in donor cells and a hyperdiploid pattern were observed in two cases, respectively, while a normal, recipient pattern was documented in the other two cases. Serial chromosome studies performed in acute leukemia patients after bone marrow transplantation may allow the detection of different chromosomal patterns of relapse. In those cases who relapsed with a cell clone cytogenetically different from the pattern at diagnosis, a direct role played by the conditioning treatment in the pathogenesis of the relapsing disease may be hypothesized.

Acute Disease↗
PubMed1987

Cytogenetic analyses in 89 patients with secondary hematologic disorders--results of a cooperative study.

Eighty-nine patients who developed a secondary hematologic disorder and were studied with chromosome analysis were collected from nine institutions. The results of the study confirmed previous findings, in particular, -5/5q-, -7/7q-, -17, and +21 were the most frequently encountered aberrations. Moreover, a t(1;7)(p11;p11) was reported in four cases and consistent chromosome abnormalities were observed in a small group of patients who had been treated only with surgery, but not with chemo- or radiotherapy for a previous tumor.

Acute Disease↗
PubMed1986

The reaction of 2-thiobarbituric acid with biologically active alpha,beta-unsaturated aldehydes.

The standard assay for lipid peroxidation is the measurement of the pink, 532 nm absorbing chromogen which is formed upon reaction of 2-thiobarbituric acid (TBA) with the lipid peroxidation product malonaldehyde (MDA). The present studies indicate that the toxic lipid peroxidation product trans-4-hydroxynonenal and its dehydration product trans,trans-nonadienal react with TBA to form chromogens which absorb maximally at 530 and 532 nm, respectively. Other biologically active alpha,beta-unsaturated aldehydes, such as acrolein and crotonaldehyde, short-chain homologs of alkenals formed during lipid peroxidation, and trans,trans-muconaldehyde, a novel diene dialdehyde, react with TBA to form products which absorb maximally at 495 nm. The molar extinction coefficients of the aldehyde:TBA chromogens formed were found to vary widely, suggesting that only small contributions to the 532 nm absorption by TBA adducts of reactive aldehydes other than MDA may be encountered during the use of the TBA assay.

Aldehydes↗