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J R Testa

Publications and source records attributed to J R Testa.

At least 181 records · Page 10Linked to original sources
PubMed1987

Minimally differentiated acute nonlymphocytic leukemia: a distinct entity.

Ten of 136 consecutive adult patients with previously untreated acute leukemia had morphologically undifferentiated leukemia by light microscopy. Leukemic cells from these patients were characterized by agranular cytoplasm, negative histochemical staining with sudan black (SB) and nonspecific esterase, and absent lymphoid cell surface markers and therefore were not classifiable according to the French-American-British (FAB) system. Electron microscopy with myeloperoxidase (MPO) staining revealed the presence of peroxidase positive cytoplasmic granules and endoplasmic reticulum in eight of the nine patients studied. Cells from the patient who was negative for MPO were also negative for platelet peroxidase. A series of monoclonal antibodies to myeloid antigens also revealed myeloid features with all patients having at least one myeloid differentiation antigen present on the surface of their cells. Common acute lymphoblastic leukemia (ALL) antigen was absent in the nine patients tested. Cytogenetic analysis of blast cells was abnormal in seven patients on whom adequately banded chromosomes were obtained although there were no consistent abnormalities. No patient had a Ph1 chromosome. Only two of the ten patients achieved a complete remission. Morphologically undifferentiated leukemia may have myeloid features when studied by transmission electron microscopy or with monoclonal antibodies for cell surface markers. Such studies should be performed when the leukemia cannot be classified using either light microscopy or lymphoid cell surface markers. Such patients infrequently achieve remission with standard therapy and constitute a distinct entity.

Acute Disease↗
PubMed1986

Unusual cytogenetic findings in two patients with t(4;11) acute leukemia.

Unusual cytogenetic findings are described in two patients with acute leukemia and rearrangements involving chromosomes 4 and 11. Both patients had clinical and phenotypic features often found in leukemia with t(4;11)(q21;q23). At initial diagnosis, one patient showed a standard t(4;11) with duplication of the 4q-translocation derivative. The latter finding has been described previously in a few patients with t(4;11) in association with disease progression. By analogy with the Ph1 chromosome in chronic myelogenous leukemia, duplication of the 4q-suggests that this derivative is the critical recombinant in the t(4;11). The second patient has a novel complex translocation, t(4;11;15)(q21;q23;q21). Analysis of this variant translocation implies that the 11q+ is the consistent chromosome rearrangement in this type of leukemia. The apparent contradiction of the findings in these and other relevant reported cases reviewed here suggests that genes on both the 11q+ and 4q- recombinant chromosomes are important, in either the etiology or the progression of this disease.

Adult↗
PubMed1986

Dicentric chromosome 17 in patients with leukemia.

A putative isochromosome of the long arm of chromosome #17 was identified in bone marrow cells from each of six patients with leukemia. Adequate sample was available for detailed study in four patients, and in each of these four cases examination with multiple staining techniques implied that the rearrangement is a dicentric chromosome, dic(17)(p11.2). An asymmetry of constriction at the two centromeric regions suggested that one centromere was inactive. The data presented here suggest that many of the presumed i(17q) markers observed in leukemia may actually represent dicentric rearrangements.

Centromere↗
PubMed1986

Detection of clonal karyotypic abnormalities in most patients with acute nonlymphocytic leukemia examined using short-term culture techniques.

Cytogenetic studies using short-term culture methods, both with and without methotrexate synchronization, were performed on 53 consecutive patients with acute nonlymphocytic leukemia. Among 50 patients with adequate specimens, 42 (84%) showed a clonal karyotypic abnormality. Numerical changes were observed in 22 cases. Chromosome #8 was most frequently gained (eight cases), whereas chromosome #7 was most frequently lost (five cases). Structural rearrangements were detected in 35 cases. A 5q- was seen in three cases, 6q- in two, 7q- in four, standard or variant t(8;21) in four, 11p- in two, t(11q23;-) in two, t(15;17) in four, inv(16) in two, and inv(20) in two. In five patients small abnormal clones were observed, which represented less than 10% of the total cells analyzed. In five other patients the sole abnormality detected was a tiny structural rearrangement. There was no significant difference in remission rate or in survival among groups of patients without clonal abnormality, with a mixture of normal and abnormal karyotypes or with only abnormal cells. Patients who showed complex karyotypes (four or more chromosomal alterations) had a very poor prognosis. In contrast, patients with t(8;21) tended to have a favorable survival outlook. A normal karyotype was associated with an intermediate prognosis.

Acute Disease↗
PubMed1986

Association of the translocation (15;17) with malignant proliferation of promyelocytes in acute leukemia and chronic myelogenous leukemia at blastic crisis.

Cytogenetic studies were performed on nine patients with acute promyelocytic leukemia. Every patient had an identical translocation (15;17) or, in one case, a variant three-way rearrangement between chromosomes 7, 15, and 17. Another patient with chronic myelogenous leukemia was examined at the time of blastic crisis when the patient's bone marrow was infiltrated by hypergranular promyelocytes and blasts. Bone marrow cells contained a t(15;17) as well as a Ph1 chromosome. Only the latter abnormality was observed in the chronic phase of the disease. The translocation (15;17) was detected in all ten patients when bone marrow or peripheral blood cells were cultured for 24 hours prior to making chromosome preparations. However, the t(15;17) was not seen in three of these same cases when bone marrow cells were processed directly. These findings indicate that the t(15;17) is closely associated with acute proliferation of leukemic promyelocytes and that detection of this karyotypic defect may be influenced by the particular cytogenetic processing method used in different laboratories. An analysis of the banding pattern in the variant translocation provided additional evidence favoring chromosomal breakpoints at or very near the junction between bands 17q12 and 17q21 and at 15q22.

Bone Marrow↗
PubMed1986

High molecular weight DNA from fixed cytogenetic preparations.

Cell pellets that have been stored in routine clinical cytogenetic fixative were studied for the presence of intact DNA. A method for the isolation of high molecular weight DNA from fixed cytogenetic preparations of human leukocytes, bone marrow, and cell hybrid cultures is presented. DNA preparations from fixed pellets were cleaved with restriction enzymes, transferred to nitrocellulose filters after agarose gel electrophoresis, and hybridized to radiolabeled probes to demonstrate that fixed cell pellets could yield DNA of sufficient quality for Southern blot hybridization analysis. This protocol may be useful for molecular analysis of DNA from fixed cell pellets of patients who are unavailable for additional sampling.

Bone Marrow↗
PubMed1985

A case of acute lymphoblastic leukemia with severe hypodiploidy.

A case of acute lymphoblastic leukemia with a severe hypodiploid chromosome constitution is reported. The modal chromosome number was 36, and the karyotype of these cells was 36,X, -X, -2, -3, -5, -7, -9, -12, -13, -15, -16, -17, -20, +21, +mar,del(1) (p13.1p22.3),inv(3)(q13.3q29). In addition to a haploid set, extra copies of chromosomes #6, #10, #14, #18, and #21 were found, as in most cases with severe hypodiploid karyotypes. A second, near-triploid cell line was also observed. An examination of chromosomal heteromorphisms suggested that the severe hypodiploid clone originated either from a near-triploid cell or from a common precursor cell.

Chromosome Aberrations↗
PubMed1985

Fluorescent bodies in lymphocytes in chronic lymphocytic leukemia.

The relative frequency of lymphocytes with nuclear Y-body-like fluorescent structures (F-bodies) was examined in ten patients with chronic lymphocytic leukemia (CLL) and in ten normal individuals. In each patient, the frequency was significantly higher as compared to that of normal controls. Female CLL patients showed a significantly higher proportion of F-body-positive (F-body +) cells than male CLL patients, whereas in normal males and females similar frequencies of F-body + cells were observed. There was no apparent relationship between the frequency of F-body + lymphocytes and the relative age of an individual. The presence of F-bodies in CLL had no obvious correlation with the presence of karyotypic abnormalities in these patients. Isolated T and B lymphocytes derived from four normal subjects showed no extra F-bodies as found in CLL patients.

Adult↗
PubMed1985

The pattern and clinical significance of karyotypic abnormalities in patients with idiopathic and postpolycythemic myelofibrosis.

Six of eight (75%) patients with postpolycythemic myelofibrosis (PPMF) and 11 of 20 (55%) patients with idiopathic myelofibrosis (MF), seen at the University of Chicago, had abnormal karyotypes in cells of bone marrow origin. The specific chromosomal findings and their clinical significance in these patients were analyzed. A review of the literature added the findings from abnormal karyotype studies in 10 patients with PPMF and 36 patients with MF to this series. The demonstration of an increased frequency of cytogenetic abnormalities after cytotoxic therapy in polycythemia vera (PV) implies that such therapy may have a role in the development of chromosomal changes seen in treated PV and PPMF. The cytogenetic abnormalities in MF appear to be unrelated to therapy except possibly for an association with partial or complete losses of chromosome 5 or 7. Trisomy 8 is the only finding that is more common in MF than in PPMF. Other abnormalities were more common in PPMF, particularly 20q-, loss of 7 or 7q-, and trisomy 9, and to a lesser extent trisomy 1q and 5q-. Cytogenetic abnormalities do not show a pattern that can be used to distinguish between PPMF and MF, nor are they useful in the prognosis of MF or in initial studies in PPMF. PPMF does appear to have a higher tendency toward leukemic transformation than does MF, and an evolution in karyotype appears to have serious prognostic implications in PPMF in regard to this transition.

Adult↗
PubMed1985

Chromosomal alterations in acute leukemia patients studied with improved culture methods.

Cytogenetic studies, using improved short-term culture techniques, were performed on 64 patients with acute leukemia to determine the incidence and kinds of clonal karyotypic changes detectable with this newer methodology. An adequate number of analyzable mitoses was obtained from 59 patients. Clonal chromosomal alterations were found in 88% (52 of 59) of patients, as compared to approximately 50% in previous studies of acute leukemia in which conventional techniques were used. From our series, abnormal karyotypes were detected in 37 of 44 (84%) cases with primary acute nonlymphocytic leukemia, all 5 with secondary acute nonlymphocytic leukemia, and all 10 with acute lymphoblastic leukemia. Among the entire group of patients, several recurrent abnormalities were observed, e.g., -7 in eight cases, +8 in seven cases, t(15;17) in four cases, and t(8;21) or a variant of this translocation in four cases. In five patients, the only abnormality was a rather subtle structural rearrangement (e.g., tiny deletion). Five other patients had clonal changes which were found in less than 10% of the mitoses examined in each case. Our results indicate that most patients with acute leukemia, both acute nonlymphocytic leukemia and acute lymphoblastic leukemia, have clonal chromosome abnormalities associated with their disease.

Acute Disease↗
PubMed1985

Double minute chromosomes in acute myeloblastic leukemia.

Two patients with acute myeloblastic leukemia (AML) with double minute chromosomes (dmins) are described. One patient had dmins in approximately one-third of bone marrow cells examined at diagnosis; no other karyotypic changes were observed. The dmins disappeared when the patient achieved a complete remission. The second patient developed acute leukemia as a second cancer, having previously received radiotherapy and chemotherapy for a breast carcinoma. At the time of diagnosis of AML, the patient exhibited dmins in 12% of bone marrow cells; other complex karyotypic changes were observed. Data on the clinical and cytogenetic features of these cases are compared with those of other reported cases of acute leukemia with dmins. The possible biologic and clinical significance of dmins in acute leukemia is discussed.

Acute Disease↗
PubMed1985

Induction of terminal differentiation and nuclear appendage(s) formation in a human myeloid leukaemia cell line (HL-60).

In vitro terminal differentiation in a female myeloid leukaemia cell line (HL-60) was induced by either of the two inducing agents, dimethylsulphoxide (DMSO) and dimethylformamide (DMF). A higher frequency of more mature myeloid cells was noted with increasing concentrations of the inducing agents up to the optimal dose limits for cell viability, and with longer post-induction incubation periods. The highest percentage of polymorphs was obtained at 8 days post-induction with 1.25% DMSO and after 6 and 8 days exposure to 90 mM DMF. A proportion of polymorphs showed non-sex specific drumstick-like nuclear appendages, which were morphologically similar to the sex-specific drumsticks found in polymorphs from normal females in vivo. The correlation between the nuclear lobe counts and the frequencies of drumstick-like appendages in polymorphs was also similar to that reported for drumsticks in blood cells in vivo. The various stages of terminal differentiation and nuclear appendage formation in polymorphs under induced differentiation were similar to those occurring in vivo. Chromosomal analyses of this cell line indicated that individual cells had lost one X chromosome, and no portion of the missing X was detected in any of the rearranged chromosomes. Since no truly sex-specific drumsticks appeared to be present in the polymorphs of this cell line containing only one X chromosome, the study supports the accepted notion that there is a correlation between drumstick frequency and the presence of one versus two X chromosomes.

Cell Differentiation↗
PubMed1984

Eosinophilic differentiation of the human promyelocytic leukemia cell line, HL-60.

HL-60 promyelocytic leukemia cells differentiated to eosinophils and eosinophilic precursors when cultured under mildly alkaline conditions (pH 7.6-7.8) for 7 d without refeeding. New cytoplasmic granules appeared blue in the least mature cells and red in the most mature cells when stained with Wright-Giemsa. The granules also stained with Luxol-fast-blue, a characteristic of eosinophil granules. Furthermore, most cells contained the eosinophil major basic protein (MBP); the Charcot-Leyden Crystal (CLC) protein (lysophospholipase), eosinophil peroxidase, acid phosphatase, and arylsulfatase were also detected in a portion of these cells. The eosinophil major basic protein was found in a high proportion of undifferentiated cells, and thus may be constituitively produced. By examining finely banded chromosomes, translocation break points were demonstrated at q22 on one chromosome 16 and at q23 on the other homologue; abnormalities in this region of the long arm of 16 are a characteristic finding in the recently described syndrome of acute myelomonocytic leukemia (AMMoL) with abnormal bone marrow eosinophils. In common with the bone marrow eosinophils in these patients, the HL-60 eosinophil granules contained chloroacetate esterase and periodic-acid Schiff (PAS) reactive material; crystalloid inclusions were rare. Therefore, the HL-60 cell line appears to be an in vitro model for eosinophilopoiesis and may be specially suited for the study of the abnormal eosinophils seen in certain malignant conditions.

Blood Proteins↗
PubMed1984

The human calcitonin gene is located on the short arm of chromosome 11.

By molecular hybridization of human calcitonin cDNA probes to DNA from human-rodent hybrid cells containing identified human chromosomes, we have mapped the human calcitonin gene to the short arm of chromosome 11. This location has been confirmed by in situ hybridization, which further localized the calcitonin gene to region 11p13-15. The significance of this region regarding gene linkage and possible markers for inherited cancers is discussed.

Animals↗
PubMed1984

Synchronization of human leukemic cells: relevance for high-resolution chromosome banding.

The cell-cycle kinetics of synchronized K562 human leukemic cells and bone marrow cells from adults with acute leukemia were studied in order to develop more reliable methods for producing increased numbers of mitoses, particularly those with elongated chromosomes suitable for high-resolution banding. Parameters examined included DNA content, mitotic index (MI), and chromosome preparations. K562 cells synchronized with methotrexate (MTX), thymidine (Tdr), or hydroxyurea (HU) showed two-fold increases in peak MI. Optimal harvesting times after release from block were approximately 10.5, 12.5, and 14.5 h for MTX, HU, and Tdr, respectively. MTX was selected for studies with cells from patients. Cells from 7 of the 10 patients studied showed 4.4-fold increases in peak MI. The optimal harvesting time was 9.5 to 11.5 h after release from block, considerably later than the 6 h time previously assumed in studies using stimulated lymphocytes. Cells from the three remaining patients showed no increase in MI after synchronization; and the lack of response may have been related to the high proportion of cells in G0+G1 prior to MTX exposure. For both the K562 cell line and most patient specimens, the combination of synchronization with appropriate release times and short Colcemid exposure (10 min) resulted in substantially improved chromosome preparations.

Adult↗