Biomedical subjects

S C Jhanwar

Publications and source records attributed to S C Jhanwar.

At least 91 records · Page 5Linked to original sources

PubMed1989

Localization of human adenosine deaminase (ADA) gene sequences to the q12----q13.11 region of chromosome 20 by in situ hybridization.

The gene for human adenosine deaminase (ADA), an enzyme constitutively expressed in all tissues investigated so far and deficient in some cases of severe combined immune deficiency, was previously assigned to chromosome 20 by syntenic analysis, using somatic cell hybrids and quantitative enzyme studies on patients with chromosome abnormalities. Attempts at regional localization of ADA through indirect approaches have so far resulted in uncertainties, as well as apparent inconsistencies. In situ hybridization of high-resolution somatic and pachytene chromosomes using a 3H-labeled cDNA probe of the ADA gene localized the gene to 20q12----q13.11. Rearrangements involving this region have been reported in various human hematological malignancies; in this regard, possible implications of the physical proximity of the ADA gene locus to that of SRC, an oncogene previously localized to the same region of chromosome 20, are briefly discussed.

Adenosine Deaminase↗

PubMed1987

Multiparameter characterization of L3 leukemia cell populations.

Multiparameter analysis of 14 consecutive patients with L3 cell populations (FAB classification) in bone marrow showed consistently high mean cellular RNA content but heterogeneity with respect to percent cels in S- and G2M-phases of the cell cycle, cell surface phenotype, cytogenetic abnormalities, cellular DNA content, and nuclear activities of terminal deoxynucleotidyl transferase. Five of the 14 patients had the characteristic profile of L3 leukemia with high RNA content, a typical t(8;14) or t(8;22) translocation, low Tdt, B-cell surface phenotype, pseudodiploid modal number of chromosomes, high proliferation and normal DNA index. The remaining 9 patients had features thought to be unusual and they were very heterogeneous. Median survival time from time of diagnosis was 115 days with no patient alive after 474 days. The survival times exhibited excellent correlation with a parametric model assuming exponential distribution. Accordingly, the presence of abnormal DI predicted for decreased, and the presence of t(8;14) or pseudodiploidy was associated with increased survival rates. However, due to the small number of patients in this study, generally applicable conclusions should be drawn only from a collection of larger numbers of cases of this rare type of leukemia.

Adult↗

PubMed1987

Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells.

An interferon-inducible cytokine, IP-10, containing homology to a family of proteins having chemotactic (platelet factor 4, beta-thromboglobulin) and mitogenic (connective tissue-activating peptide III) activities has been mapped to chromosome 4 at band q21, a locus associated with an acute monocytic/B-lymphocyte lineage leukemia that exhibits the nonrandom translocation t(4;11)(q21;q23). In situ hybridization of t(4;11)(q21;q23)-carrying leukemic cells revealed that the IP-10 gene is proximal to the breakpoint of this translocation. No DNA rearrangement was evident when the IP-10 gene was hybridized to genomic DNA isolated from two patients' leukemic cells that contain t(4;11)(q21;q23). However, restriction fragment length polymorphism in the 5' region of the IP-10 gene was detected. The ETS1 protooncogene is located at 11q23 and is known to translocate to chromosome 4 in t(4;11) (q21;q23) and into the interferon gene cluster in (9;11) (p22;q23). Both translocations are associated with acute monocytic leukemia. These results suggest a model in which juxtaposition of genetic loci regulated by antiproliferative signals, such as interferon, next to an oncogene, like ETS1, could effectively short circuit homeostatic control circuits and contribute to the neoplastic state.

Blood Proteins↗

PubMed1987

Host origin of the human hematopoietic microenvironment following allogeneic bone marrow transplantation.

The origin of marrow stromal cells post allogeneic bone marrow transplantation (BMT) was studied. Two groups of patients receiving HLA-identical marrow grafts from sex mismatched siblings were included in the study: the first group (eight patients) received conventional marrow grafts and the second group (ten patients) received stromal cell and T cell depleted grafts. All patients showed hematopoietic engraftment with donor cells. Marrow aspirates obtained from these patients were used to establish stromal layers in long-term marrow cultures (LTMC) for 4 to 6 weeks. In both groups, karyotype analysis of nonhematopoietic cultured stromal cells showed host origin even as late as day 760 posttransplantation. Immunofluorescence methods using monoclonal antibodies against components of fibroblasts, macrophages, and endothelial cells, showed that the composition of stromal layers was similar to those obtained from normal controls. Our data indicate that marrow stromal progenitors capable of proliferation are nontransplantable and do not originate from a hematopoietic-stromal common progenitor.

Adolescent↗

PubMed1987

Intermediate- to high-grade histology of lymphomas carrying t(14;18) is associated with additional nonrandom chromosome changes.

We describe additional nonrandom chromosome abnormalities in 18 cases of intermediate- to high-grade non-Hodgkin's lymphoma (NHL) bearing t(14;18) that were ascertained in a prospective cytogenetic study of all lymphomas seen at Memorial Hospital during the period January 1, 1984, to December 31, 1986. These included seven cases that had histological evidence of transformation from a lower grade and 11 that lacked such evidence. The most common of the additional changes seen in both groups affected chromosomes 6 and 7 and comprised the loss of chromosome 6 or del(6q) and the presence of more than two copies of chromosome 7 or duplication of 7q. Changes affecting these two chromosomes were less frequent in low-grade lymphomas with t(14;18) as well as in lymphomas lacking the translocation. These data suggest that common cytogenetic mechanisms underlie expression of high-grade histologies by lymphomas carrying t(14;18). In addition, they may serve as indicators of transformation when encountered in low-grade lymphomas with t(14;18).

Adult↗

PubMed1987

Cytogenetic and histologic correlations in malignant lymphoma.

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.

Chromosome Aberrations↗

PubMed1986

In situ localization of human fibronectin (FN) genes to chromosome regions 2p14----p16, 2q34----q36, and 11q12.1----q13.5 in germ line cells, but to chromosome 2 sites only in somatic cells.

The locations of the genes for fibronectin (FN) on chromosomes of human germ line and somatic cells were determined by in situ molecular hybridization with two 3H-labeled DNA probes, one for the region encoding the cell attachment domain of human FN, the other for the 3' noncoding and part of the coding region. Pachytene chromosomes of two males and lymphocyte chromosomes of one of these males and a female were used. Two regions of hybridization on pachytene and somatic chromosome 2 (p14----p16 and q34----q36) were found, but not in all individuals. A third region of hybridization was found at 11q12.1----q13.5 in meiotic, but not with significant frequency in somatic chromosomes. It is not clear if these differences between meiotic and somatic chromosomes, and the large differences between individuals at some of the other hybridization sites, resulted solely from technical factors. The differences between the findings in meiotic and somatic preparations might be due to the presence of four strands in pachytene chromosomes versus only one per somatic chromatid. Individual differences in DNA sequences in the chromosome segment containing the gene, differences in gene locations among individuals, or between meiotic and mitotic chromosomes might account for the other findings. The results confirm some of the earlier studies with cell hybrids that mapped FN genes to chromosomes 2 or 11. The combined findings suggest that some of these loci may be coding for the plasma form of FN and others for the cellular form. The expression of the different FN types by differentiated cells might then depend on the loci that are activated.

Chromosome Banding↗

PubMed1986

Physical mapping of the factor VIII gene proximal to two polymorphic DNA probes in human chromosome band Xq28: implications for factor VIII gene segregation analysis.

Genomic DNA segments for the coagulation factor VIIIc gene (F8C), which exhibits only limited restriction length polymorphism, map to the proximal region of band Xq28 by somatic cell hybridization analysis and in situ hybridization. Using somatic cell hybrids, we have obtained data which place probes DX13 (used to detect locus DXS15) and St14 (used to detect DXS52) distal to F8C, within band Xq28. Previous studies have mapped the factor IX gene (F9) and probe 52A (used to detect DXS51) proximal to F8C, in Xq26----q27 and Xq27, respectively (Camerino et al., 1984; Drayna et al., 1984; Mattei et al., 1985). Thus, the relative order of genetic marker loci in the Xq27----qter region is most likely cen-F9-DXS51-F8C-(DXS15, DXS52)-Xqter. The collection of these molecular probes is thus potentially useful in three-factor crosses of factor VIII gene segregation.

Animals↗

PubMed1986

The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22----q24.

We report the chromosomal localization of the cellular oncogene SKI, the putative oncogene of the Sloan-Kettering viruses (SKVs), a group of transforming retroviruses that had been isolated from chicken embryo cells infected with the avian leukosis virus tdB77. Southern blot analysis of DNA from mouse X human somatic cell hybrids with the v-SKI probe established synteny with chromosome 1, but excluding the region 1pter----q21. In situ hybridization of the same probe both to human spermatocyte pachytene and lymphocyte metaphase chromosomes enabled precise localization of the gene to the region 1q22----q24, a region that frequently is involved in translocations and other rearrangements in diverse human tumor types. In situ hybridization studies of metaphase spreads from a small noncleaved cell lymphoma that exhibited a t(1;14)(q21;q32) translocation showed that SKI translocates to the der(14) chromosome. Cytogenetic analysis of 65 prospectively ascertained non-Hodgkin's lymphomas revealed that the SKI region undergoes nonrandom breakage leading to translocations. Further analysis of the chromosome breaks in this group of lymphomas suggested that those involving the SKI site probably are of importance in tumor progression.

Animals↗

PubMed1985

Definitive chromosomal location of the H-2 complex by in situ hybridization to pachytene chromosomes.

Chromosome 17 of the mouse carries the H-2 complex and the T/t complex. An understanding of the organization of this region and an accurate genetic map of chromosome 17 would be of great value for both immunologists and developmental biologists. Until now the only maps available have been derived solely from recombinational studies using several translocations, an inherently inaccurate method. We have found the definitive location of the H-2 complex by the use of in situ hybridization. Our results show that both the T/t complex and the H-2 complex map to positions far more distal than the generally accepted map positions. This proves that recombination in Robertsonian chromosomes underestimates physical map distances on chromosome 17.

Animals↗

PubMed1985

Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin.

The chromosomal localization of genes for parathyroid hormone (PTH), beta-globin cluster, c-Ha-ras-1, and insulin, all of which have previously been assigned to the short arm of chromosome 11, generated considerable interest because of their association with development of disease states. Furthermore, the availability of recombination data from family studies made the determination of their physical location on the chromosome necessary. Several investigators have attempted this; however, controversy has arisen concerning the location of beta-globin, insulin, and c-Ha-ras-1 genes. Thus, while the results of some investigators suggested that all three genes are situated in the 11p15 region, data of other investigators placed the beta-globin and insulin genes close to the centromere and c-Ha-ras-1 in a more proximal region than 11p15. The subchromosomal position of the PTH gene remains to be determined. We have performed in situ hybridization of meiotic pachytene bivalents with 3H-labeled cloned genomic probes of PTH, beta-globin, and insulin genes and find their germ-line positions to be the following: PTH at 11p11.21, beta-globin at 11p11.22, and insulin at 11p14.1. These data, when considered with our recent germ-line assignment of the c-Ha-ras-1 gene to 11p14.1, indicate the following relative order on 11p: cen-PTH-beta-globin-c-Ha-ras-insulin or cen-PTH-beta-globin-insulin-c-Ha-ras. The former order is consistent with genetic evidence from linkage analysis of DNA polymorphisms adjacent to these genes segregating in families.

Chromosome Mapping↗

PubMed1985

Germ-line chromosomal localization of human C-Erb-A oncogene.

The human germ-line position of c-erb-A, the cellular counterpart of v-erb-A, has been determined by in situ molecular hybridization of a 3H-labeled c-onc gene probe to meiotic pachytene chromosomes. Both v-erb-A and v-erb-B are the v-onc genes that are associated with induction of sarcoma and erythroblastosis in chicken by the avian erythroblastosis virus, a rapidly transforming RNA tumor virus. The position of c-erb-A, determined here to be at 17q21.33-q22, is in the same region of chromosome 17 in which a nonrandom break occurs in the generation of t(15;17), a translocation commonly seen in acute promyelocytic leukemia.

Chromosome Mapping↗

PubMed1985

13-cis-Retinoic acid does not increase the true remission rate and the duration of true remission (induced by cytotoxic chemotherapy) in patients with chronic phase chronic myelogenous leukemia.

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Adolescent↗

PubMed1984

Localization of the cellular oncogenes ABL, SIS, and FES on human germ-line chromosomes.

The human germ-line positions of the oncogenes ABL, SIS, and FES, the cellular counterparts of the v-onc genes of Abelson murine leukemia virus, simian sarcoma virus, and feline sarcoma virus, respectively, have been determined by in situ molecular hybridization of 3H-labeled v-onc gene probes to meiotic pachytene chromosomes. The position of ABL at 9q34.1 corresponds to the breakpoint in chromosome 9 in the translocation that gives rise to the Philadelphia chromosome, t(9;22) (q34; q11); the position of SIS at 22q13.1 is distal to the breakpoint in this chromosome. FES at 15q26.1 is also distal to the breakpoint in chromosome 15 in the translocation commonly seen in acute promyelocytic leukemia, t(15;17) (q24;q22).

Abelson murine leukemia virus↗

PubMed1984

Properties of myelofibrosis-derived fibroblasts.

Fibroblasts derived from bone marrow of patients with primary myelofibrosis and of patients with other well-differentiated myeloproliferative disorders without myelofibrosis (MPD), exhibit in vitro the same properties as fibroblasts derived from normal bone marrow. The cell density distribution, cell sedimentation rate distribution and time-dependent adherence of bone marrow fibroblast colony-forming cells (CFU-F) of MPD patients are similar to those of normals. The in vitro growth parameters, namely anchorage, serum dependence, and contact inhibition are analogous in fibroblasts derived from fibrotic and normal bone marrow. The intra- and extra-cellular distribution of fibronectin, type I, type III and type V collagens is similar in cultured marrow fibroblasts from normals, and from MPD patients with and without myelofibrosis. The plasminogen-dependent fibrinolytic activity elicited from normal and myelofibrotic marrow fibroblasts are equivalent. Moreover, marrow fibroblasts from patients with myelofibrosis do not exhibit the chromosomal abnormalities present in hematopoietic cells. These observations provide strong evidence for the absence of changes associated with neoplastic states in fibroblasts derived from fibrotic bone marrow, and support the hypothesis that myelofibrosis associated with MPD results from the abnormal interaction between hematopoietic cells and marrow collagen-producing cells, rather than from a primary disorder affecting the latter cells.

Animals↗

PubMed1984

Progression of nodular poorly differentiated lymphocytic lymphoma to Burkitt's-like lymphoma.

Histologic conversion of nodular lymphomas to more aggressive patterns has been well described and occurs in 15% to 40% of cases. Most conversions have involved changes from nodular to diffuse patterns and often from small to larger cell types. Conversions to undifferentiated lymphomas, but not specifically to the Burkitt's type, have infrequently been described. This report describes three cases of nodular poorly differentiated lymphocytic lymphoma that converted to a Burkitt's-like lymphoma. Conversion was associated with short survivals, increasing lactate dehydrogenase (LDH) levels, and changes in DNA stemline, RNA content, and S-phase values, as determined by flow cytometry. Karyotypes in two cases revealed a t(14;18). Surface immunoglobulin could be demonstrated on transformed Burkitt's-like cells from lymph node in one case, but in none of the cases on cells from bone marrow.

Adult↗

PubMed1983

Chromosome abnormality in a human TCGF-dependent T-lymphocyte culture generated against autologous melanoma cells in vitro.

Six T-cell growth promoting factor (TCGF)-dependent T-cell cultures and phytohemagglutinin-stimulated peripheral blood lymphocytes from a patient with metatastic malignant melanoma were karyotyped. Three of the TCGF-dependent cultures were noncloned, started after in vitro sensitization against autologous malignant melanoma cells in tissue culture. A fourth was a subculture of one of these. The two remaining T-cell cultures were generated by in vitro sensitization of the same individual's lymphocytes against allogeneic Epstein-Barr virus-transformed B-cell lines. One of the cultures (AV7) and its subculture (AV/LDP39) showed a 17q+ anomaly in 100% of metaphases studied. All other TCGF-dependent T-cell cultures and fresh blood lymphocytes had normal karyotypes. The possible mode of origin of the abnormality and its significance are discussed.

Adult↗

PubMed1983

Non-T, non-B acute lymphoblastic leukemia (L3) with t(8;22) and two 14q+ chromosomes.

A patient with L3 leukemia is reported whose leukemic cells were characterized cytogenetically by a duplication of the long arm segment 1q25 leads to q42, trisomy for chromosome 7, t(8;22)(q24;q11), and two 14q+ chromosomes. Immunologic marker analysis revealed the leukemic cells to be of the non-T, non-B ("null") type. This observation, when considered in conjunction with a previous report of heterogeneity in cell lineages of L3 leukemias, raises the possibility of some lymphoid neoplasms arising in stem cells.

Adult↗