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Biomedical subjects

A M Block

Publications and source records attributed to A M Block.

8 recordsLinked to original sources

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

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

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

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

[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