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M Blick

Publications and source records attributed to M Blick.

At least 55 records · Page 3Linked to original sources
PubMed1987

Molecular analysis of interferon-induced suppression of Philadelphia chromosome in patients with chronic myeloid leukemia.

Treatment with recombinant human interferon alpha-A (Roferon-A) is associated with stable suppression of the population of cells that display the Philadelphia (Ph1) chromosome in some patients with chronic myelogenous leukemia (CML) as defined by cytogenetic analysis. Southern blot analyses employing a 3' breakpoint cluster region (bcr) probe (Pr-1) were performed to confirm a complete suppression of the Ph1+ chromosome-positive clone of cells at the DNA level. The complete disappearance of rearranged restriction fragments of the bcr gene, which were a characteristic of the disease prior to Roferon-A therapy, was accompanied by the restoration of normal bone marrow and achievement of durable ongoing complete remission for 9 and 6 months, respectively, in two patients with Philadelphia-positive (Ph1+) CML. Molecular analysis is a valuable probe for monitoring the clinical course of disease in patients with Ph1+ CML.

Adult↗
PubMed1987

Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia.

The aberrant abl protein product of a chronic myelogenous leukemia (CML) blast crisis cell line (K562) and of five Philadelphia chromosome-positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of v-abl and a region within the third exon of the breakpoint cluster region (bcr) respectively. Both the anti-abl and anti-bcr sera detected a 210 kd band in extracts derived from K562 cells and from two CML patients with myeloid blast crisis. p210 was detected by the anti-abl but not the anti-bcr sera in three CML patients with myeloid (one patient) and lymphoid (two patients) blast crisis, indicating the absence of bcr exon 3 in this protein. Southern blot analysis on DNA derived from one of the patients in the latter group was consistent with the break on chromosome 22 occurring 5' to bcr exon 3. Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr-abl protein with at least two molecular variants, both of which are enzymatically active as protein kinases.

Blast Crisis↗
PubMed1987

Proto-oncogene expression in human normal bone marrow.

We and other investigators have previously reported our findings on oncogene expression in human leukemia in an attempt to study the possible involvement of these genes in the leukemic state. An important shortcoming of these studies has been the lack of information on the expression of these genes in normal hematopoietic cells. To address this question we analyzed both the transcript size and level of expression of six oncogenes in fresh hematopoietic cells obtained from hematologically normal individuals and compared the results to those found in fresh samples obtained from patients with various forms of leukemia (acute myelogenous leukemia, acute lymphocytic leukemia, and chronic myelogenous leukemia). We found low level expression of c-myc, c-myb, c-fes, and c-raf in normal bone marrow in sharp contrast to the high levels of expression found in some forms of leukemia. C-fos was highly expressed in both normal bone marrow and certain leukemias. We were unable to detect c-sis expression in our normal samples. With the exception of c-fes, there was no variation in transcript size when comparing normal and leukemic samples. Having defined the transcript sizes and levels of expression for these proto-oncogenes in normal hematopoietic cells, we know that aberrant transcript size for the genes we have studied is not a common event in leukemias. The levels of expression, however, vary widely between normal hematopoietic cells and leukemia as well as between different types of leukemia.

Actins↗
PubMed1986

c-K-ras codon 12 GGT-CGT point mutation. An infrequent event in human lung cancer.

Hu-c-ras represent a family of oncogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point mutations observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and therefore is not likely to play a major role in cancer development.

Cell Transformation, Neoplastic↗
PubMed1986

Differential expression of metastasis-associated cell surface glycoproteins and mRNA in a murine large cell lymphoma.

A metastatic variant cell subline of the Abelson virus-transformed murine large lymphoma/lymphosarcoma RAW117 has been selected in vivo ten times for liver colonization. Highly metastatic subline RAW117-H10 forms greater than 200 times as many gross surface liver tumor nodules as the parental line RAW117-P. Analysis of cellular proteins and glycoproteins indicates reduced expression of murine Moloney leukemia virus-associated p15, p30, and gp70, and increased expression of a sialoglycoprotein, gp150, in the highly metastatic H10 cells. Northern analyses of oncogene expression suggested that mRNA of various oncogenes was expressed equally or not expressed in the RAW117 cells of differing metastatic potential. Differential gene expression was examined using a cDNA library of 17,600 clones established from poly A+ mRNA isolated from H10 cells. The cDNA library was screened by the colony hybridization technique using probes made from both RAW117-P and -H10 cells. Approximately 99.5% of these cDNA clones were expressed identically in P and H10 cells. Of the few differentially expressed cDNA clones (approx. 150/17,600), one-half of these were identified as Moloney leukemia virus sequences in a separate probing with a radiolabeled Moloney leukemia virus probe. The remainder of the differentially expressed mRNA detected by colony hybridization of the cDNA library were expressed at higher levels (approx. 1/6) or lower levels (approx. 1/3) in the highly metastatic H10 cells.

Animals↗
PubMed1986

Rearrangement and enhanced expression of c-myc oncogene in fresh tumor cells obtained from a patient with acute lymphoblastic leukemia.

Both enhanced and altered expressions of cellular oncogenes have recently been implicated in specific forms of human malignancy (for review: [2, 8]). The fact that certain human tumors have characteristic chromosomal translocations has led to the hypothesis that specific cellular oncogenes may be 'activated' in these genetic recombinations. In a number of human undifferentiated B-cell lymphoma (UBL) cell lines carrying the t(8:14) translocation it has been shown that the human c-myc gene is located on the region of chromosome 8 (8q24), which is translocated to the immunoglobulin heavy-chain (IHC) locus on chromosome 14 [7, 24]. We report here the molecular cloning of the recombination site between c-myc and IHC in fresh uncultured cells obtained from a patient with rapidly progressive and fatal acute lymphoblastic leukemia. The translocation was associated with an enhanced c-myc expression in the tumor cells of this patient.

Base Sequence↗
PubMed1986

C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies.

Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c-sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in

Humans↗
PubMed1985

Detection of a surface antigen on NIH3T3 cells transfected with a human leukemia oncogene.

This study was conducted to examine the cell surface changes associated with oncogene induced transformation. Using the transfection technique the DNA of a human acute lymphocytic leukemia (ALL) was used to transform murine NIH3T3 cells. Balb/c mice were immunized with these transfectants and their immune splenocytes were used to produce a monoclonal antibody (17-9H3). Antibody 17-9H3 was demonstrated to bind to the cell membranes of transfectants and leukemia cells but not normal 3T3 cells in an enzyme linked immunosorbent assay. Fresh human leukemias, cultured leukemia lines and normal hemopoietic cells were examined with immunoperoxidase staining techniques to determine the specificity of 17-9H3. Our data suggest that the antigen associated with a human acute lymphocytic leukemia oncogene is ubiquitous, distributed among both neoplastic and normal hemopoietic cells. Among fresh human leukemias the antigen appears to be present primarily on fresh null ALLs and chronic myelogenous leukemia (CML) in blast crisis. This antigen was also found to be expressed by the majority of cultured T-cell lines tested.

Animals↗
PubMed1985

Heterogeneity of non-Hodgkin's lymphoma probed by nucleic acid cytometry.

Flow cytometric analyses of cellular DNA, RNA, and double-stranded RNA content were performed on lymph nodes and extranodal tissue from 177 patients with non-Hodgkin's lymphoma. With increasing histologic grade, a higher incidence of aneuploidy, higher proliferative activity, and higher total and double-stranded RNA content were found. Despite considerable cytometric heterogeneity within histologic grades and morphologic subdivisions, conformity between cytometric and morphologic classifications was observed in 85% of cases. Among intermediate-grade and high-grade lymphomas, increased proliferative activity and diploidy were associated with more frequent responses to treatment. Thus, nucleic acid-derived parameters relate to morphologic subtypes and permit an objective approach to lymphoma classification based on ploidy, proliferation, and RNA characteristics that also had prognostic implications.

Aneuploidy↗
PubMed1984

Oncogene expression in human leukemia.

The transforming genes of retroviruses (v-onc) are derived from normal cellular genes referred to as proto-oncogenes. These cellular genes have the capacity for conversion to oncogenes (c-onc) that are capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in human leukemia, we have analyzed their expression in a variety of fresh samples. We found that a number of oncogenes are expressed in different leukemic types and that although the transcript size did not vary for each gene, the copy number did. The myc gene (2.4 kb transcript) and the rasHa gene (1.5 kb transcript) were universally expressed. But in contrast to rasHa, the myc signal intensity varied. Myb (4.5 kb transcript) was expressed in all samples except B cell diseases. We detected low levels of abl expression (multiple mRNA species) in all leukemic types analyzed. Sis gene (4.2 kb transcript) expression was restricted to one patient sample with chronic myelogenous leukemia in blast transformation.

Acute Disease↗
PubMed1978

Ovarian (corpus luteum) hemorrhage during anticoagulation therapy.

Corpus luteum hemorrhage is a complication of long-term anticoagulant therapy that has rarely been reported in the literature. Within 16 months, we saw six cases in which young women taking anticoagulants to prevent clotting of prosthetic heart valves suffered corpus luteum hemorrhages. Diagnosis was difficult and delayed. Medication stopped the bleeding in three patients; bilateral salpingo-oophorectomy was necessary in the remaining three. Our patients had great difficulty controlling their anticoagulant therapy and had histories of previous bleeding episodes. We believe corpus luteum hemorrhage may become more common as more premenopausal women undergo cardiac valvular surgery.

Adult↗
PubMedDate not supplied

In vitro analysis of cell populations involved in Hodgkin's disease lesions and in the characteristic T cell immunodeficiency.

Hodgkin's disease (HD) is an aggressive human lymphoproliferative disease that displays a curious pleomorphic histopathologic appearance unlike that of any of the common non-Hodgkin's lymphomas (NHL). Although the bizarre giant cells of the HD lesion, the Reed-Sternberg cells (RSC) and mononuclear variant Hodgkin's cells (HC), have been considered to be malignant cells, little objective evidence supports this conclusion. We have studied the proliferative characteristics of T cell as well as RSC and HC-enriched populations from HD lesions, and found the majority of the proliferative activity in the T cell populations. RSC-enriched populations not only showed little spontaneous proliferation, but also did not respond to a variety of cytokine growth factors in vitro, suggesting that these cell populations are not actively growing cells. Further molecular studies to identify possible monoclonal T or B cell populations in HD lesions, using a TCR beta chain probe and IgH probes respectively on Southern blot analysis, revealed no evidence of monoclonal lymphoid cell populations. Additional studies on the characteristic T cell immunodeficiency in HD were also undertaken. Our previous studies had associated a decrement in IL-2 production with this defect. Our studies now show that an intrinsic T cell abnormality exists when HD patients' T cells are stimulated with agonistic MAb that can optimally activate and stimulate IL-2 production in normal control T cells.

Adolescent↗
PubMedDate not supplied

Expression of abl and other oncogenes is independent of metastatic potential in Abelson virus-transformed malignant murine large cell lymphoma.

The role of oncogene expression in tumor metastasis was examined using the Abelson leukemia virus-transformed murine large cell lymphoma RAW117. Cell sublines of low and high metastatic potential expressed equally abl oncogene-coded mRNA and its phosphoprotein product p160, and the capacity of p160 to become autophosphorylated with gamma-[32P]ATP was the same among low and high metastatic cells. The expression of other oncogene-coded mRNAs (fos, myc, myb), if present, was also similar in low and high metastatic RAW117 cells. Although oncogene expression is thought to be important in initiating, and in some cases maintaining, the transformed phenotype, its expression in RAW117 lymphoma cells appears to be unrelated to metastatic phenotype.

Abelson murine leukemia virus↗
PubMedDate not supplied

A novel c-abl protein product in Philadelphia-positive acute lymphoblastic leukaemia.

Activation of cellular proto-oncogenes as a result of chromosomal abnormalities has been implicated in the development of some human malignancies. Perhaps one of the most striking examples of this association occurs in chronic myelogenous leukaemia, where the Philadelphia (Ph) translocation results in substitution of the 5' end of the c-abl proto-oncogene with bcr gene sequences. A unique hybrid bcr-abl message is produced. As the Ph translocation is also present in some patients with acute lymphoblastic leukaemia, we initiated studies to determine if similar genomic events occur in these two different forms of Ph-positive leukaemia. Here we report that the Ph translocation in acute lymphoblastic leukaemia can result in production of a novel aberrant c-abl protein that is distinct from the bcr-abl protein found in Ph-positive chronic myelogenous leukaemia. Our observations suggest that alternative mechanisms of activation of c-abl exist, and may be important in the development of human acute lymphoid rather than chronic myeloid malignancies.

Electrophoresis, Agar Gel↗
PubMedDate not supplied

Analysis of the estrogen receptor gene structure in human breast cancer.

We studied the structure of the human estrogen receptor (ER) gene by Southern blot analysis in 34 tumor samples and normal breast tissues or peripheral blood samples from the same patients. No rearrangement or amplification of the ER gene was seen in either ER-positive or ER-negative breast tumors. One patient showed an apparent constitutional deletion of a non-allelic ("invariant") restriction fragment in DNAs from both normal leukocytes and bilateral breast tumors. Of 20 patients constitutionally heterozygous for an ER gene RFLP, only one showed tumor-specific loss of heterozygosity. This is consistent with the ER gene change we noted overall. At the c-myb locus on chromosome 6q adjacent to the ER gene, allele loss occurred in 1 out of 15 informative cases. In addition, tumor-specific allelic loss at the c-H-ras1 locus on chromosome 11p occurred in 4 of 22 informative cases, and at the D17S28 locus on chromosome 17p in 2 of 7 informative cases.

Alleles↗
PubMedDate not supplied

Oncogene expression in adenocarcinomas of the colon and in colon tumor-derived cell lines.

Six colon cancer cell lines, 13 colon tumors and ten normal colon tissues were analyzed for RNA expression using probes for c-myc, c-k-ras, c-myb, and c-fos and for the p53, TGF-alpha, and EGF receptor genes. No aberrant transcripts were detected. Levels of expression in tumors ranged from two-fold below that of normal tissue when the v-fos probe was used to 10 fold above the normal level when the c-myc probe was used. Enhanced c-myc expression was also observed in the cell lines. Southern and DNA dot blot analyses revealed c-myc amplification in three of the six cell lines.

Actins↗