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Biomedical subjects

A M Block

Publications and source records attributed to A M Block.

14 recordsLinked to original sources
PubMed2001

Truncated STAT proteins are prevalent at relapse of acute myeloid leukemia.

Signal transducer and activator of transcription (STAT) proteins are implicated in the control of cell survival, proliferation and differentiation in response to hematopoietic cytokines. C-terminally truncated STAT isoforms (STATbeta), as opposed to the full length form (STATalpha), have a competitive or even transdominant negative effect on gene induction mediated by the STAT pathway. We have previously demonstrated that while constitutively active STAT proteins were detected in ten of 36 (28%) for STAT3 and eight of 36 (22%) for STAT5 in pretreatment samples from newly diagnosed acute myeloid leukemia (AML) patients, a significantly larger fraction of samples [21 of 27 (78%)] expressed STATbeta proteins. To determine whether STATbeta expression was maintained or increased after relapse in AML, we compared STAT activity and isoform expression at diagnosis and at relapse in 17 patients. In this selected group, constitutively active STAT3 was detected in 13 of 17 (76%) AML samples at diagnosis but was detected in only four of these patients at relapse. Constitutively active STAT5 was detected in three of 17 (18%) AML samples at diagnosis; but only two at relapse. In contrast, STATbeta protein expression was observed in 12 of the 17 pretreatment samples (71%) and in 16 of 17 samples at relapse. Only one patient did not express STATbeta at relapse. Our results suggest that STATbeta isoform expression, rather than level of constitutive activity, may be involved in disease progression in AML.

Adult↗
PubMed1998

Association of germline p53 mutation with MLL segmental jumping translocation in treatment-related leukemia.

Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of the ABL and/or MLL oncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL segmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLL gene, consistent with segmental jumping translocation. A genomic region including CD3, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML.

Acute Disease↗
PubMed1996

Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia.

The AML1/ETO fusion transcript is expressed in virtually all patients with t(8;21) (q22;q22) acute myeloid leukemia (AML). The fusion transcript can be detected by reverse transcription-polymerase chain reaction (RT-PCR) in most of these patients in long-term complete remission (CR) following conventional chemotherapy or autologous bone marrow transplantation (BMT). However, AML1/ETO expression has not been analyzed in a series of patients following allogeneic BMT. We examined CR bone marrow (BM) samples and, in some cases, blood samples from 10 patients with t(8;21) leukemia who underwent allogeneic BMT in either first or second remission or first or second relapse. A variety of myeloablative regimens were used. Eight patients received non-T-cell depleted BM from matched sibling donors, one patient received a T-cell depleted haploidentical BM, and one patient received a non-T-cell depleted BM from a matched unrelated donor (MUD). Five patients developed acute and/ or chronic graft versus host disease (GVHD). The furthest time points analyzed for the AML1/ETO transcript in the 10 patients in CR following allogeneic BMT ranged from 7.5 to 83.0 months. Sufficient RNA was extracted from the most recent BM or BM and blood samples from nine patients to assay for presence or absence of the AML1/ETO fusion transcript by RT-PCR. The fusion transcript was detected by RT-PCR in all nine of these patient samples; eight were positive in BM and one was negative in BM, but positive in blood. The fusion transcript could not be detected in a BM sample from the tenth patient obtained 7.5 months after BMT, but the amount of RNA available was suboptimal. Hematopoietic chimerism could be demonstrated in sorted CD34+ BM cells from two of four patient CR BM samples with RT-PCR evidence of the fusion transcript. Additionally, in one of the two cases with chimerism, we demonstrated an abnormal clonal population of recipient cells in the CR BM sample by fluorescence in situ hybridization. One patient died of complications from GVHD, while the other nine patients remain alive without evidence of relapse, with a median follow-up time of 27 (range, 7.5 to 87) months post-BMT. These data suggest that allogeneic BMT, like conventional chemotherapy and autologous BMT, is not sufficient to eradicate cells expressing AML1/ETO, and that a positive RT-PCR for the fusion transcript post allogeneic BMT is compatible with continued CR.

Adult↗
PubMed1993

Establishment and characterization of the tumors of chronic lymphocytic leukemia cell line in nude and SCID mice.

A new cell line, designated MO1043, was established from the peripheral blood (PB) of a patient with B-cell chronic lymphocytic leukemia (CLL). Both the PB leukemia cells and MO1043 were found to have an abnormal cytogenetic marker of trisomy 12, the most common cytogenetic abnormality in CLL. In addition, both the PB cells and MO1043 expressed a cell surface phenotype of typical B-CLLs. The MO1043 was efficiently transplanted into X-irradiated athymic nude mice by i.p. inoculation after it was subjected to serial passages in new born (1 week old) and irradiated adult nude mice. The tumor of a CLL cell line (termed CLL tumor) was also generated in the nude mice by s.c. inoculation of the cells. The MO1043 was inoculated i.p. into mice with severe combined immunodeficiency (SCID) which had not been subject to any preconditionings. The CLL tumor in the non-conditioned SCID mice was disseminated to various tissues in a manner more analogous to CLL tumors in patients as compared with nude mice, where the CLL tumors were not as widely disseminated. At each of four different tumor doses, i.e. 2 x 10(6), 6 x 10(6), 1.8 x 10(7) and 5.4 +/- 10(7) cells of MO1043, the transplantability was 100%. Titration experiments revealed a reciprocal relationship between survival and the number of tumor cells inoculated. FACS analysis showed that several cell surface markers of the parental MO1043 were maintained in CLL tumors from nude and SCID mice. Fluorescence in situ hybridization with novel DNA probes demonstrated that CLL tumors of both nude and SCID mice maintained trisomy 12. The CLL tumor models developed here, particularly the SCID mouse model, may be very useful for therapeutic studies of CLL.

Aged↗
PubMed1991

Cloning of the t(11;14)(q13;q32) translocation breakpoints from two human leukemia cell lines.

The t(11;14)(q13;q32) translocation has been associated with several subtypes of human leukemia and lymphoma. It has been proposed that this translocation activates a proto-oncogene designated BCL1. In an effort to better understand the mechanism by which this translocation leads to malignancy, we have studied this translocation in two human cell lines. MO1094 and MO2058 were derived from patients with prolymphocytic variants of chronic lymphocytic leukemia. Southern blotting of the MO2058 cell line documented that the translocation linked the Jh region in the immunoglobulin heavy chain gene to the previously described BCL1 major translocation cluster (MTC). Using the polymerase chain reaction, we cloned this translocation and showed that the chromosome 11 breakpoint was within 7 bp of two other samples reported previously. Southern blotting of the MO1094 cell line suggested that the translocation in this cell line might link Jh sequences to a new region in the BCL1 locus on chromosome 11. Therefore, the MO1094 breakpoint was cloned from a genomic library. Comparison with normal cloned DNA from the BCL1 locus showed that the chromosome 11 breakpoint occurred 24 kb telomeric of the MTC. This work reinforces the concept that translocation breakpoints in the BCL1 locus are scattered over at least 63 kb.

Base Sequence↗
PubMed1990

Expression of the multidrug resistance gene in myeloid leukemias.

The human multidrug-resistance gene (MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy.

Adult↗
PubMed1988

Sister chromatid exchange and chromosome abnormalities in uremic patients.

Chronic renal failure heightens the risk of malignancy. We therefore examined lymphocytes from 44 uremic patients and 24 normal controls for chromosome abnormalities and sister chromatid exchange (SCE) rate. This is the first report of SCE in uremia. Uremia was found to increase structurally abnormal chromosomes and elevate the rate of SCE. These cytogenetic changes in uremia may play a role in the heightened risk of cancer.

Adult↗
PubMed1988

Cytogenetic studies in chronic lymphocytic leukemia, prolymphocytic leukemia and hairy cell leukemia: a progress report.

We studied the B lymphocyte metaphases in 78 of 94 cases of CLL, 24 of our 28 hairy cell leukaemias, 4 CLL's which transformed into prolymphocytic leukaemia and 8 original prolymphocytic leukaemias. Twelve CLL's were carriers of trisomy 12, 13 of this trisomy 12 with other abnormalities and 15 had other abnormalities without trisomy 12. Trisomy 12 seemed to be more frequent in patients with CLL or prolymphocytic leukaemia with a monoclonal gammopathy. In contrast to our previous results, the isolated finding of a trisomy 12 had an influence on the median survival.

Chromosomes, Human, Pair 12↗
PubMed1987

[Devic's optic neuromyelitis. 4 cases].

We report 4 cases of neuromyelitis optic (Devic's disease), with 3 to 7 year-follow-up for 3 of them. Most of the data agreed with the previously reported cases: subacute onset, association of optic neuritis and myelitis within several weeks or months, absence of relapse, good prognosis for paraplegia but poor prognosis for visual loss, and effectiveness of corticosteroids on spinal cord involvement in 4 cases. Moreover these 4 cases have revealed the following rare features: unilateral visual disturbance (1 case), total recovery of visual signs (1 case) with only a short period of follow-up, onset during childhood (1 case), onset following an acute lymphocytic meningitis (1 case), and dependency from corticosteroid therapy (2 cases). None of the patients had obvious immunological disturbance. N.M.R. imaging revealed in 2 cases, disseminated demyelinated areas which confirmed neuropathological data from the literature, showing that anatomical lesions could be wider than expected on clinical signs. The poor visual prognosis, the serum inflammatory signs, the epidemiologic data, the high cell and protein levels in C.S.F., and the absence of relapse suggested, in our cases and in most of the previously reported ones, that neuromyelitis optic must be differentiated from multiple sclerosis.

Adrenal Cortex Hormones↗
PubMed1982

Sexual dysfunction of the male with diabetes mellitus.

The literature states that 40 to 60 percent of males with diabetes will at some time become impotent. Nursing awareness and intervention in this problem can make a positive impact on the sexual functioning of males with diabetes. This article supplies suggestions for nursing care of males with diabetes mellitus and autonomic neuropathic impotence. Included is a description of the problem, including incidence, clinical morphology, description of normal male sexual functioning, pathogenesis, differential diagnosis, psychotherapeutic and surgical interventions. Nursing intervention includes a section on counseling by the nurse practitioner.

Autonomic Nervous System Diseases↗