Increased lymphoblast-like cells following umbilical cord blood stem cell transplantation do not predict recurrent acute leukemia.
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Acute Disease↗
Biomedical subjects
R McGlennen
Publications and source records attributed to R McGlennen.
Oestrogen receptor transcripts associated with cervical human papillomavirus infection.
OBJECTIVE: Studies have been inconsistent in establishing sex steroids as a risk factor for human papillomavirus (HPV) infections. This study was designed to determine whether cervical oestrogen receptors (as measured by oestrogen receptor transcripts) at the cervix would be associated with cervical HPV infections. METHODS: In 175 women, ages 14-44, we tested for the presence of HPV DNA and oestrogen receptors transcripts at the cervix during routine pelvic examinations. All subjects completed a self administered questionnaire regarding sexual and menstrual histories. RESULTS: 40% of the women (n=70) tested positive for HPV at the cervix. Of those women testing positive for HPV, 99% had detectable levels of Oestrogen receptors transcripts (n=69/70). HPV cervical infections were independently associated with presence of Oestrogen receptors transcripts (OR=39.8, CI=4.4, 361.1) and greater numbers of sexual partners (OR=1.1, CI=1.01, 1.18). CONCLUSION: Women who expressed higher levels of oestrogen receptors transcripts were significantly more likely to have cervical HPV infection. These results demonstrate that Oestrogen receptors may play an important part in cervical HPV infections.
Adolescent↗
Graft-versus-leukemia is sufficient to induce remission in juvenile myelomonocytic leukemia.
It has been unclear whether a graft-versus-leukemia (GVL) effect assists in the control of juvenile myelomonocytic leukemia (JMML) following allogeneic bone marrow transplant. We describe a patient with JMML who relapsed early after an unrelated donor transplant, and following withdrawal of immunosuppression developed graft-versus-host disease (GVHD). Associated with GVHD the proportion of donor cells measured by variable nucleotide tandem repeat (VNTR) analysis increased, and peripheral blasts and cutaneous disease were eliminated. These findings strongly suggest that GVL has a role in the control of JMML.
Bone Marrow Transplantation↗
MLL gene rearrangement, cytogenetic 11q23 abnormalities, and expression of the NG2 molecule in infant acute myeloid leukemia.
To study prognostic factors in infant acute myeloid leukemia (AML), we analyzed 44 children treated on Childrens Cancer Group protocols for MLL gene rearrangement by Southern blot, cytogenetic 11q23 abnormalities, and reactivity with monoclonal antibody 7.1. This antibody detects the human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, which has previously been reported to be expressed on human melanoma. NG2 has been found to be expressed on human leukemic blasts but not on other hematopoietic cells. In childhood AML, NG2 cell surface expression correlated with poor outcome and with some but not all 11q23 rearrangements. In childhood acute lymphoblastic leukemia, NG2 expression correlated with poor outcome and with balanced 11q23 translocations. In this study, 29 of 44 (66%) of infants with AML showed MLL rearrangement and, as expected, this group had a high incidence of French-American-British M4/M5 morphology (22/29). Of the cases tested, 35.1% (13/37) were NG2 positive. All (13/13) NG2-positive cases were rearranged at MLL, whereas only 46% (11/24) of NG2-negative cases had MLL rearrangement. NG2 expression did not correlate with poor outcome (P = .31); there was a trend towards a worse outcome with MLL rearrangement (P = .13). Thus monoclonal antibody 7.1 does not detect all cases of MLL rearrangement in infant AML.
Acute Disease↗
B-cell gene rearrangement in benign and malignant lymphoid proliferations of mucosa-associated lymphoid tissue and lymph nodes.
The polymerase chain reaction (PCR) with polyacrylamide gel electrophoresis was used to study patterns of immunoglobulin heavy chain (IgH) gene rearrangement (GR) in formalin-fixed, paraffin-embedded specimens of lymphomas and reactive conditions of mucosa-associated lymphoid tissue (MALT) and lymph node. DNA amplification was performed directly on sections obtained from paraffin blocks. Five patterns of PCR products were observed: a single band, two or more discrete bands, smearing, a single band overlying a smear, and two or more bands over a smear. A pure polyclonal pattern (smear) was observed in all of the reactive lymph nodes but in only 15% of cases of Helicobacter pylori (HP) gastritis with lymphoid hyperplasia, 25% of cases of HP gastritis without lymphoid hyperplasia, and 37% of colonic specimens of various types. Patterns consisting of multiple bands with or without background smearing were common in gastritis, colitis, and gastric lymphomas. Single bands or dominant bands were present in all lymph node and salivary gland lymphomas, 12 of 14 cases of gastric lymphoma, and 17 of 20 cases of HP gastritis with lymphoid hyperplasia. These bands were reproducible in deeper sections from the same paraffin block or similar areas sampled in different blocks in all of the lymph node and salivary gland lymphomas, 11 of 12 gastric lymphomas, but only 1 of 17 cases of HP gastritis with lymphoid hyperplasia. Bands were also found in 3 of 20 cases of HP gastritis without lymphoid hyperplasia and 17 of 38 colonic specimens, but these were not reproducible. The complexity of patterns of IgH GR in acquired MALT compared with lymph nodes may be the result of a relative paucity of B-cell clones or preferential proliferation of B-cell clones with a limited area of distribution.
DNA, Neoplasm↗
Polyclonal engraftment after unrelated donor bone marrow and cord blood transplantation.
Data on a small number of allogeneic sibling donor marrow transplants have indicated that reconstituted hematopoiesis can be oligoclonal or even monoclonal, suggesting that hematopoiesis can be reconstituted from a very small number of stem cells. However, other studies have failed to confirm this observation. Animal data indicate that hematopoiesis is likely to be oligoclonal after transplantation using limiting numbers of hematopoietic stem cells, or in cases of poor engraftment. In this study we investigated clonality of engraftment after unrelated donor (URD) bone marrow (BM) and cord blood transplantation, clinical settings in which human leukocyte antigen (HLA) disparities have been known to impair engraftment and in which stem cell numbers have been limiting. Twenty-four URD transplant recipients (20, BM; 4, cord blood) together with 8 sibling donor marrow, 2 sibling donor peripheral blood stem cells (PBSC), and 1 sibling donor cord blood recipients were studied at 28 days, 100 days, 6 months, and 1 year post-bone marrow transplantation (BMT) using the polymerase chain reaction (PCR)-based human androgen receptor assay (HUMARA) as a marker of clonality. URD marrow and cord blood recipients show polyclonal reconstitution in all cases, and results are similar at early and late time points after BMT. Similar results were seen in sibling donor marrow and cord blood recipients. These data indicate that oligoclonal hematopoiesis is not a frequent event after URD stem cell transplantation, even for cases in which limited numbers of stem cells are infused.
Adolescent↗
Molecular diagnosis of cystic fibrosis.
The clinical and pathologic features of patients with cystic fibrosis are summarized, and generalized genotype or phenotype correlations are discussed in this article. Incorporation of modern molecular biologic techniques into a rapid, cost-efficient, and specific diagnostic laboratory test is outlined. The protocol for the multiplex polymerase chain reaction detection of five common cystic fibrosis transmembrane conductance regulator (CFTR) mutations by ASO hybridization is detailed. Neonatal screening and issues involved in the genetic counseling of families at risk for cystic fibrosis are presented. Recommendations for molecular diagnostic testing in cystic fibrosis are made.
Base Sequence↗
Phorbol ester-induced surface transferrin receptor modulation. No correlation with decreased cell proliferation.
Both phorbol ester or diacylglycerol (DAG) reduce cell surface transferrin receptor (TFR) number in CEM cells (a human T-cell acute lymphoblastic leukemia line) and HL-60 cells (a human promyelocytic leukemia cell line). This effect occurs with a t1/2 of approx. 30 min and is mimicked by addition of phospholipase C to cell cultures. Although cell surface TFR number is reduced to 25-30% of the control level 5 h after phorbol ester administration, apparent cell proliferation (as measured by [3H]thymidine incorporation) remains unaffected. Although independent of extracellular calcium (EGTA is slightly enhancing), the phenomenon is completely blocked by 30-min pretreatment with the calcium channel blocker diltiazem. Dilitazem pretreatment, while preventing receptor redistribution, does not completely block the phorbol ester-induced increase in TFR phosphorylation thought to be associated with receptor redistribution. Thus, calcium channel blockade effectively dissociates the effects of tetradecanoylphorbol acetate (TPA) on TFR internalization and phosphorylation. Our results also demonstrate that phorbol ester-induced effects on the TFR can be mimicked by the endogenous stimulator of protein kinase C, DAG, whether added directly to cultures or produced by the cells in response to exogenous phospholipase C. Furthermore, the phenomenon of TFR redistribution here described is not associated with a decreased proliferative capacity.
Cell Division↗