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J R Testa

Publications and source records attributed to J R Testa.

At least 199 records · Page 11Linked to original sources
PubMed1984

Promyelocytic blast crisis in chronic granulocytic leukemia with 15;17 translocation.

A patient with Philadelphia chromosome Ph1-positive chronic granulocytic leukemia (CGL) developed an acute transformation associated with a hemorrhagic diathesis and bone marrow infiltration by hypergranular promyelocytes and blasts. Cytogenetic analysis of bone marrow metaphase cells at transformation showed a t(15;17) superimposed upon the Ph1-positive cell line. These findings suggest a critical relationship between the t(15;17) and arrest of myeloid leukemic cell differentiation at the promyelocyte stage.

Adult↗
PubMed1984

Centromere spreading in acute nonlymphocytic leukemia.

Centromere spreading (CS) was observed in bone marrow chromosomes from a patient with acute myeloblastic leukemia (AML), prior to therapy. The abnormality was found in a direct specimen, in a 24-hr culture, and in a culture treated with the methotrexate synchronization technique. A small hypodiploid clone, 45,XY,-19, was also observed. This case provides further evidence that CS can occur in acute nonlymphocytic leukemia (ANLL). The possible relationship between CS and hypodiploidy in this and other reported cases of ANLL is discussed.

Aged↗
PubMed1984

Abnormalities of chromosome 16 in association with acute myelomonocytic leukemia and dysplastic bone marrow eosinophils.

Six patients with M4 acute myelomonocytic leukemia ( AMMoL ) were identified who had abnormalities of chromosome 16 in bone marrow cells. Five had a pericentric inversion, inv(16)( p13q22 ), and a sixth patient had a translocation, t(16;16)(p13.1;q22). Each of these six patients had bone marrow eosinophils that were abnormal in morphology on light and/or electron microscopy and by cytochemical stains. The eosinophils constituted 1%-24% of nucleated marrow cells. Of 61 acute nonlymphocytic leukemia (ANLL) patients, all those with AMMoL and abnormal bone marrow eosinophils had an inv(16) or a t(16;16). One other patient in this group had a rearrangement of chromosome 16 (with a break in the short arm at band p13); however, the ANLL type was M1 and no abnormal eosinophils were present. Four patients with ANLL types other than M4 had an increase in marrow eosinophils; three in whom the eosinophils appeared normal and one with ANLL-M2 and bizarre eosinophils morphologically distinct from those seen in AMMoL . Chromosome pair 16 was normal in the latter four patients. AMMoL with dysplastic bone marrow eosinophils appears to represent a unique clinicopathologic entity associated with several related abnormalities affecting 16q . The morphologic features of both blasts and eosinophils may be more important than the absolute number of eosinophils in the marrow in identifying this group of patients. This may have prognostic importance as five of six patients achieved complete remission with standard antileukemic therapy and are still alive.

Adult↗
PubMed1984

Acquired chromosome rearrangements, including fine interstitial deletions, in a patient with Down syndrome and monoblastic leukemia.

A female child with Down syndrome who developed acute monoblastic leukemia is reported. Anemia associated with milk leukopenia was first recognized when the patient was 14 months old. Acute monoblastic leukemia was diagnosed 1 year later; cytogenetic studies were performed on circulating leukemic cells at this time. Analysis of elongated, finely banded chromosomes revealed three structural rearrangements, including two rather subtle interstitial deletions, in addition to trisomy 21 which was representative of the patient's constitutional karyotype. The karyotype of the leukemic cells was 47,XX,+21,t(3;18)(p23;q11.2), del(7)(q31.1q31.3), del(9)(p22p24 or p21p23). The patient received no cytostatic chemotherapy and died 4 months after the diagnosis of acute leukemia was made.

Child, Preschool↗
PubMed1984

Cytotoxic and cytodifferentiative components of 6-thioguanine resistance in HL-60 cells containing acquired double minute chromosomes.

As an experimental strategy for potentially dissociating and studying the cytotoxic and cytodifferentiative antileukemic effects of 6-thioguanine (6-TG), cultured human promyelocytic leukemia cells (HL-60) were serially selected for growth in increasing concentrations of 6-TG (0.5 to 50 micrograms/ml). Three acquired characteristics, cytotoxic resistance, cytodifferentiative resistance, and double minute chromosomes (DM), were monitored at successive 6-TG selection levels. Approximately 200-fold resistance to the cytotoxic effect of 6-TG was acquired at the first selection step, and it neither increased at higher 6-TG selection levels nor reverted to greater sensitivity in cells subcultured off of drug. This was due to the irreversible loss of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. In contrast, a lesser, not completely quantifiable, degree of resistance developed to the cytodifferentiative effects of the purine nucleobases hypoxanthine and 6-TG which varied as a function of 6-TG selection pressure. Numerous DM, not observed in the parental wild-type HL-60 cells, appeared at 6-TG (0.5 micrograms/ml) selection which varied substantially in parallel with 6-TG selection pressure up to 6-TG (20 micrograms/ml). At higher selection levels (50 micrograms/ml or prolonged culture on 20 micrograms/ml), a marked decrease in DM occurred which was associated with the acquisition of new marker chromosomes. The most consistent marker was a chromosome 6 with additional material in the short arm (6p+); this was noted as a single copy in the basal 6-TG/20 subline but as two copies (trisomy 6; 2p+) in independently selected higher 6-TG-resistant subcultures. These cytogenetic findings suggest the presence of amplified genes which increased in number and shifted from a predominance in extra-chromosomal DM to intrachromosomal sites as a function of 6-TG selection. Among the 6-TG-resistant sublines, there was no change or a decrease in the amplification level of the known amplified oncogene c-myc from that demonstrated in parental HL-60 cells. Although proof requires detailed analyses with specific gene probes, the overall results imply that: (a) the cytotoxic component of the resistance is due to an invariant loss of HPRT which, therefore, is not likely to be related to amplified genes; (b) the cytodifferentiative component of the resistance is due to a positively selectable mechanism which could be directly or indirectly related to 6-TG-selected amplified genes; and (c) variations in the cytogenetic indicators of amplified genes and the resistance to 6-TG cannot be simply ascribed to quantitative variations in c-myc amplification.

Animals↗
PubMed1984

Unusual karyotypic changes and B cell involvement in a case of lymph node blast crisis of chronic myelogenous leukemia.

A patient with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) entered a blast crisis localized to lymph nodes. On light microscopy, by morphology and histochemical staining, the blasts were undifferentiated. In spite of terminal deoxynucleotidyl transferase positivity, some of the lymph node cells expressed a myeloid differentiation antigen, OKM1, and were peroxidase positive by transmission electron microscopy (TEM). However, the majority of cells were peroxidase negative on TEM and expressed OKT-10, a marker found on both primitive myeloid and lymphoid cells. Cultures of lymph node cells stimulated with Epstein-Barr virus or lipopolysaccharide (LPS) revealed the Ph1, indicating B cell involvement in the CML. T cells from cultures stimulated with L4-phytohemagglutinin and T cell growth factor were negative for the Ph1. In unstimulated lymph node cells, the uncomplicated Ph1 could not be demonstrated; instead, a unique complex karyotype involving a masked Ph1 was identified in these and the LPS cultures. This karyotype was not found in bone marrow (BM) metaphase cells. Instead, BM cells showed either the simple Ph1 or the Ph1 with a rearrangement involving chromosomes 13 and 20. The patient had transient responses to three chemotherapy regimens, two of which were designed to treat acute lymphocytic leukemia, but he died 8 months after disease acceleration without BM blast crisis. These findings are compatible with an extramedullary blast crisis originating in a primitive cell with both myeloid and lymphoid characteristics.

Adult↗
PubMed1983

A variant 8;21 translocation in acute myeloblastic leukemia.

A three-way rearrangement involving chromosomes 1, 8, and 21 was observed in bone marrow cells from a female with acute myeloblastic leukemia, subtype M2 (AML-M2). The translocation break points in chromosomes 8 and 21 were identical to those found in the standard t(8;21) that is associated with this disease type. A review of this and four previously reported cases involving variant 8;21 translocations indicates that a consistent pattern of exchange may be involved in these complex rearrangements even though the third chromosome affected may differ.

Adult↗
PubMed1983

The predictive value of initial cytogenetic studies in 148 adults with acute nonlymphocytic leukemia: a 12-year study (1970-1982).

When leukemic blood or marrow specimens from 148 adults with newly diagnosed acute nonlymphocytic leukemia (ANLL) were studied with chromosome banding techniques, 79 were found to have clonal abnormalities. Among 130 treated patients, the 53 with initially normal karyotypes had a significantly longer survival rate than the 16 in whom no normal metaphases were observed (p = 0.02). The 55 patients with both normal and abnormal metaphase cells had an intermediate survival. Once a complete remission had been attained, however, there was no significant difference in median survival between those patients with entirely normal karyotypes and those with abnormal karyotypes. Among the various FAB morphologic subsets of ANLL, the differences in complete remission rate and overall survival between the various cytogenetic subsets were greatest in acute myelogenous leukemia (AML, M1 + M2). The presence of an abnormal clone was a more important predictor of clinical outcome (p = 0.02) than the presence of normal stem cell clones. Aneuploidy alone (hyperdiploidy or hypodiploidy) was not of predictive value, indicating that the use of banding techniques to identify structural rearrangements in pseudodiploid cells was essential. Clonal chromosomal abnormalities were nonrandom and acquired, and specific abnormalities were closely associated with specific clinical-pathologic subsets of ANLL. All 13 patients with acute promyelocytic leukemia and adequate cytogenetic specimens had t(15;17); this translocation was not found in any other subset of ANLL. Six patients with AML (M2) had t(8;21) or a variant of this rearrangement. Seven patients had inv(16)(p13q22) associated with acute myelomonocytic leukemia (AMMoL, M4) and abnormal marrow eosinophils. Two patients had ins(3;3) and thrombocytosis. Four patients had a translocation involving 11q, but none of these had acute monocytic leukemia (AMoL, M5); no patient had del(11q).

Acute Disease↗
PubMed1983

Near-tetraploid clones in acute leukemia.

Near-tetraploid clones were observed in bone marrow (BM) samples from two patients with acute leukemia. One case had a hypotetraploid clone (model chromosome range, 88-90) characterized by two apparently identical 8:21 translocations and loss of both Y chromosomes as well as by other changes. As in aneuploid patients with only a single 8:21 translocation, the cytologic features in this case were characteristic of acute myeloid leukemia with maturation. The marrow of the second patient contained immature leukemic blasts indicative of acute myeloid leukemia. The abnormal clone in this patient contained 93 chromosomes with an extra small marker. In this case we examined BM preparations that were made by several different cytogenetic methods: "direct" and 24-hr culture (with or without methotrexate synchronization). We scanned 100 consecutive mitotic cells from each of the three preparations and found almost no variation in the incidence of abnormal metaphase cells. However, in this particular case, we noted some disparity between preparations with respect to the quality of diploid mitoses versus that of near-tetraploid mitoses. This finding is discussed with near-tetraploid mitoses. This finding is discussed with regard to bias in selecting metaphase cells for banding analysis in acute leukemia in general. In both of our patients there was a close correlation between the incidence of polyploid mitoses observed in cytogenetic preparations and the incidence of bizarre blast cells found in BM smears on the same date.

Adult↗
PubMed1983

Variation amongst K562 cell cultures.

K562 cell cultures were obtained from three laboratories (A, B and C) outside our institution, and were designated according to source as K562A, K562B or K562C. The cultures obtained were constitutive or "wild type" K562 cell cultures, not cloned sublines. These cell cultures were compared with respect to growth kinetics, cell surface protein markers, surface antigens, cytogenetics and hemoglobin production. Morphology, growth kinetics in liquid suspension culture, cloning efficiency in soft agar culture, binding of anti-K562 monoclonal antibodies, and the majority of cell surface proteins were generally similar. In contrast, several important differences were observed: (1) hemoglobin synthesis induced by hemin was significantly different among K562A, B and C, K562A being most sensitive (P less than 0.05); (2) whereas more than 90% of K562A or C cells appeared to be Philadelphia chromosome (Ph1)-positive, less than 15% of K562B cells contained a Ph1; (3) membrane proteins (93 and 85 kilodalton) were identified in K562A, whereas only the 93 kilodalton protein was detected in K562B and neither of the proteins were detected in K562C. Our results indicate that K562 cells maintained in different laboratories can undergo tangible changes which may influence experimental results obtained in studies using these cells.

Autoradiography↗
PubMed1982

Response to 5-azacytidine in patients with refractory acute nonlymphocytic leukemia and association with chromosome findings.

Fifteen patients with acute nonlymphocytic leukemia (ANLL) who either had a relapse after a previous complete remission (nine patients) or progressive disease after initial induction attempts with combination chemotherapy (six patients) were treated with 5-azacytidine. Five patients (33%) achieved a complete remission (CR); of these, three had a relapse and died 30, 35, and 38 weeks after 5-azacytidine therapy was begun. Two patients are still alive at 39 and 138 weeks. Chromosomes were analyzed at the time of diagnosis; ten patients had a normal karyotype and five had an abnormal karyotype. Three of the five CR patients had an abnormal karyotype initially. Two of these individuals had a translocation of chromosomal material from a No. 8 chromosome to a No. 21 chromosome, t(8;21); this particular translocation has been associated with a better prognosis than have other types of chromosomal abnormalities in patients with ANLL. Even when abnormal chromosomes are present, 5-azacytidine can induce complete remission in patients with previously treated ANLL.

Adult↗
PubMed1982

Variant Philadelphia chromosome translocations in two patients with chronic myelogenous leukemia.

Two patients with chronic myelogenous leukemia and new variant Philadelphia chromosome translocations are reported. In one case, a 41-year-old male, a 10;22 translocation was found in all bone marrow cells examined. Furthermore, the Y chromosome was missing in 90% of the analyzed metaphase cells. In the second patient, a 22-year-old male, all the marrow cells contained a complex rearrangement involving chromosomes No. 2, 9 and 22.

Adult↗
PubMed1982

Correlation of occupation and karyotype in adults with acute nonlymphocytic leukemia.

Seventy-four adult patients with acute nonlymphocytic leukemia (ANLL) were classified retrospectively as to whether or not they had had occupational exposure to insecticides, chemicals and solvents, or petroleum products. Fifty-eight patients were considered nonexposed and 16 were considered exposed. The chromosome banding pattern was abnormal in 37 of the 74 patients (50%). Twenty-five of the 58 (43%) nonexposed patients had a clonal chromosome abnormality, compared with 12 of the 16 (75%) exposed patients (p = 0.02). Only 2 of 23 (8.7%) females with an abnormal karyotype were exposed, whereas 10 of 14 (71%) males with an abnormal karyotype were exposed. Either a -5/5q- or a -7/7q- was present in 67% of the exposed patients with a chromosome abnormality, compared to 28% of the aneuploid nonexposed patients. The -7/7q- abnormality was present in 7 of the 12 (58.3%) exposed patients, versus 5 of the 25 (20%) nonexposed patients with abnormal karyotypes (p less than 0.05). The -5/5q- anomaly was observed in 4 of the 12 (33%) exposed patients and in 4 of the 25 (16%) nonexposed abnormal patients. Our study supports the observation that a subset of patients with ANLL de novo have a history of occupational exposure and a unique pattern of chromosome abnormalities.

Acute Disease↗
PubMed1981

Karyotypic patterns and their clinical significance in polycythemia vera.

We studied a series of 34 polycythemia vera (PV) patients to determine the incidence of chromosome abnormalities and their relationship to leukemic transformation. Metaphase chromosomes from bone marrow or unstimulated peripheral blood were examined with conventional stain and, in 20 patients, also with banding techniques. The overall incidence of clonal abnormalities in first samples was 44% (15 of 34 patients), with a higher incidence in patients who had received prior therapy. The most frequent abnormalities were long-arm deletion of No. 5 (5q-; four patients), gain of all or most of a No. 8 (five patients), gain of all or most of a No. 9 (four patients), and long-arm deletion of No. 20 (three patients); these sometimes occurred in combination. Some of the PV patients who had cytogenetic abnormalities early in the disease have had long survivals without developing leukemia. For example, one patient has been 48,XX,+8,+9 in sequential samples obtained over the last 15 years. Five patients developed acute myeloblastic leukemia (AML); each had a complex chromosomal pattern. Two of these five patients were cytogenetically normal during the polycythemic phase; the change in karyotype occurred with the leukemic transformation. Three AML patients were studied only in the leukemic phase. Three AML patients had a 5q-, and a fourth showed loss of a B-group chromosome. Evolutionary changes in the karyotype during the disease course and the occurrence of a 5q- appear to be associated with a terminal phase of PV.

Adult↗
PubMed1981

Methods of processing marrow samples may affect the frequency of detectable aneuploid cells.

Karyotypes were analyzed from 14 patients with various myeloproliferative disorders who had marrow samples processed directly and cultured in various ways. Eleven patients had acute nonlymphocytic leukemia (ANLL) (seven patients) or a dysmyelopoietic syndrome (four patients). All of these patients were known to have an abnormal karyotype, and in each case, two samples of a bone marrow aspirate were available: one processed directly and another cultured for 24 hr. Five of the 11 patients had essentially the same proportion of abnormal cells in the direct and 24-hr samples; in five other patients, the percentage of aneuploid cells in the sample cultured for 24 hr was higher than that in the direct preparation. A higher percentage of aneuploid cells was observed in the direct preparation in only one case. In three other cases of ANLL, a marrow aspirate was cultured with methotrexate in addition to samples processed directly and after 24-hr culture; only two of these had an abnormal clone in any sample. The results of karyotype analysis differed in these two patients. The proportion of aneuploid cells was substantially higher in the methotrexate culture than in the 24-hr culture in one patient; in the other patient, the 24-hr culture contained aneuploid cells, whereas the methotrexate culture showed none. Three of the 13 aneuploid patients would have been incorrectly classified as being karyotypically normal on the basis of the initial analysis of the direct preparation, since only a single abnormal cell was detected in each case. The karyotypic pattern in untreated patients with ANLL has prognostic significance; therefore, the method of processing marrow aspirates may substantially influence the degree of correlation between the karyotype and survival reported by different laboratories.

Aneuploidy↗