Biomedical subjects

M Ffrench

Publications and source records attributed to M Ffrench.

At least 19 recordsLinked to original sources

PubMed1996

Interviewer effects on epidemiologic diagnoses of posttraumatic stress disorder.

In an epidemiologic study of 641 interviewed subjects in the Australian Vietnam Veterans Health Study, three diagnoses of Vietnam combat-related posttraumatic stress disorder (PTSD) were obtained: lifetime prevalence using a variant of the Diagnostic Interview Schedule and lifetime and current (1-month) PTSD prevalence using the Standardized Clincical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third Revision. Prevalence estimates using the Standardized Clinical Interview varied according to interviewer characteristics (female vs. male, clinician vs. nonclinician) but not for the Diagnostic Interview Schedule. The authors use a simple variant of logistic regression to distill estimates of two informative parameters characterizing interviewers' judgments: severity threshold (related to the individual interviewer's criterion of "caseness") and reliability (related to degree of classification error of the individual interviewers). Examination of these estimates shows that female clinicians adopted lower severity thresholds for diagnosis of PTSD than other interviewers and hence had higher prevalence estimates while being relatively reliable in their judgments. Examination also shows that nonclinician interviewers can perform at least as reliably as clinicians. The Diagnostic Interview Schedule measure of PTSD was not moderated by these interviewer aspects. This use of threshold and reliability parameters is offered for routine use in epidemiologic field studies to examine potential interviewer effects.

Australia↗

PubMed1996

Timed sequential chemotherapy for advanced acute myeloid leukemia.

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1-3, etoposide on days 8-10 and cytarabine on days 1-3 and 8-10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38-55%) of refractory patients and 78% (CI: 70-86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7-19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6-20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.

Acute Disease↗

PubMed1996

Cyclin-dependent kinase inhibitors (CKIs) and hematological malignancies.

Cell proliferation control is ensured by a group of proteins named cyclin-dependent kinases (CDKs), the activation of which is dependent on phosphorylation and cyclin association. In parallel, these CDKs are negatively controlled by two distinct groups of inhibitory proteins, the cyclin-dependent kinase inhibitors (CKIs). The first group, including p16Ink4a, p15Ink4b, p18Ink4c and p19Ink4d, is specific for the G1 CDKs, CDK4 and CDK6, inhibiting the kinase activity of cyclin D/CDK4-CDK6 complexes on pRb. p16Ink4a, down-regulated by pRb, inhibits G1 CDKs by competition with cyclin D; p15Ink4b, the synthesis of which is induced by TGF beta, seems to be a mediator of TGF beta-mediated cell cycle arrest. Furthermore, p18Ink4c inhibits CDK6 phosphorylation and activation by CAK. The second CKIs family is constituted by p21Waf1, p27Kip1 and p57Kip2. Their inhibitory action concerns a large range of cyclin/CDK complexes involved in G1 and S phase. p21Waf1, induced in part by p53, is up-regulated by senescence, DNA damage and cellular differentiation. p21Waf1 forms quaternary complexes with CDKs, cyclins and PCNA. Its inhibitory action, preventing CDK from phosphorylation, depends on the stoichiometry of the components. As p15Ink4b, p27Kip1 causes late G1 cell cycle arrest after TGF beta treatment and contact inhibition. The implications of CKIs in hematological malignancies are function of deletions or mutations of their genes. p16Ink4a and p15Ink4b genes, localized on 9p21, present frequent homozygous deletions in ALL T, ATL and lymphoblastic acutisation of CML. The other CKIs present very rare homozygous deletions or mutations, particularly p21Waf1 and p27Kip2. However, reduction of inhibitory activity due to hemizygous deletions might favour leukemogenesis.

Cyclin-Dependent Kinases↗

PubMed1996

Differential expression of cell proliferation regulatory proteins in B- and T-lineage acute lymphoblastic leukaemias.

In order to better understand the molecular background of differences between the clinical picture of T- and B-lineage ALLs, we studied the expression of several proteins involved in the regulation of cell proliferation in bone marrow blast cells from 30 cases of previously untreated acute lymphoblastic leukaemia (ALL); 14 cases were T- and 16 B-cell lineage ALLs. We studied several cyclin-dependent kinases (cdk1, cdk2, cdk4, cdk6) and cyclins (cyclin A, cyclin B1, cyclin D3 and cyclin E). We also studied proliferating cell nuclear antigen (PCNA) and Bcl-2 expression, the latter protein known to be involved in the prolonged survival of B-lineage ALL blasts. Proteins obtained from cell lysates were resolved on polyacrylamide gel followed by immunodetection and densitometry of specific bands. Expression of cdk1 and PCNA, markers of proliferative activity, was significantly higher in T- than in B-lineage ALL. Cdk6, which was highly correlated to PCNA, was also higher in T-cell ALL. In contrast, B-lineage ALL displayed a higher expression of anti-apoptotic protein Bcl-2. We hypothesize that those particularities may reflect differential roles of cell multiplication and apoptosis in the neoplastic proliferation of B- and T-lineage ALL.

Adult↗

PubMed1996

The Australian Vietnam Veterans Health Study: I. study design and response bias.

BACKGROUND: The Australian Vietnam Veterans Health Study was set up to examine the post-war health of former soldiers 20 or more years after service and to examine the relation of combat exposure to physical and mental health. METHOD: A prospective cohort study of a simple random sample of 1000 male Australian Army Vietnam veterans used information gathered from Army records, from personnel interview and questionnaires. Military records were used to examine response bias by determining the differences between 641 interviewed veterans, 50 known deceased veterans and 309 non-respondents (including 48 refusers and 213 non-traceable). RESULTS: Differences were evident between respondents and non-respondents, with logistic regression modelling pointing to pre-enlistment employment, antisocial behaviour, intelligence and post-Vietnam AWOL (absent without leave) as the most important discriminants with non-respondents performing worse. Compared to respondents, deceased left school earlier, had higher rank in Vietnam and at discharge, had a higher overall number of charges but not a higher rate overall, and were less likely to have gone AWOL. Deceased also received more casualty reports than respondents and non-respondents, were better behaved during service, and were better emotionally adjusted than non-respondents. Respondents compared with the Australian population had equivalent or better current socioeconomic status. CONCLUSION: There seems little bias due to non-response, but deceased tend to come from and older cohort than in the other two groups.

Adult↗

PubMed1996

The Australian Vietnam Veterans Health Study: II. self-reported health of veterans compared with the Australian population.

BACKGROUND: Self-reported physical health status of Australian Vietnam veterans was determined 20-25 years after the war and its relation to combat was investigated. METHOD: An epidemiological cohort study of a simple random sample of Army veterans posted to Vietnam between 1964 and 1972 was conducted with personal interviews using the Australian Bureau of Statistics Health Interview Survey questionnaire to compare veterans with the Australian population and a 21-item combat exposure index used to measure the relationship of combat to physical health. RESULTS: Veterans reported greater health service usage and more recent health actions than population expectations. They also reported excess health problems in almost all recent illness disease categories except endocrine conditions and cardiovascular conditions; only 6 of 37 chronic disease groups were not elevated compared to the population. Adjustment for non-response changed estimates only slightly. Combat exposure was significantly related to reports of recent and chronic mental disorders, recent hernia and chronic ulcer, recent eczema and chronic rash, deafness, chronic infective and parasitic disease, chronic back disorders and symptoms, signs and ill-defined conditions. CONCLUSION: Combat exposure may have significantly increased reports of only some health problems. A general position to complain as a result of psychological conditions due to combat is not consistent with the lack of relationship between combat and reports of physical conditions.

Adult↗

PubMed1996

The Australian Vietnam Veterans Health Study: III. psychological health of Australian Vietnam veterans and its relationship to combat.

BACKGROUND: Self-reported psychiatric status of Australian Vietnam war veterans was determined 20-25 years after the war and its relation to combat was investigated. METHOD: A simple random sample of Australian Army Vietnam veterans was interviewed nationally using standardized interviews and self-completion tests to assess the prevalence of lifetime and current psychiatric illness and its relationship to combat. Army records were used to extract data on the cohort for use in regression-based adjustment for non-response. RESULTS: The conditions mainly affecting the Australian veterans were alcohol abuse or dependence, post-traumatic stress disorder, somatization disorder were significantly related to combat exposure but not with posting to a combat unit. Less than half of the current one-month diagnoses were related to combat, possibly because of low power conferred by the relative rarity of these conditions. CONCLUSIONS: The results confirm a range of psychological problems in former warriors may linger 20 or more years from their war exposure and may be directly affected by exposure to war trauma.

Australia↗

PubMed1996

Australian Vietnam veterans: factors contributing to psychosocial problems.

OBJECTIVE: The objective of the present paper is to present comprehensive models of the current psychosocial morbidity of Australian Vietnam veterans. Seldom has research in this area attempted to 'untangle' direct and indirect influences on current functioning via possible pre-army, Vietnam and homecoming pathways. METHOD: The Australian Vietnam Veterans' Health Study gathered data on a sample of 641 veterans throughout Australia drawn randomly from army Vietnam tour lists of the era. The data arose from interview and army records of the era, and fall into four temporal categories: pre-army, Vietnam service, homecoming after Vietnam, and current state. Path analysis models of the veterans' current psychological morbidities and social wellbeing are used to identify direct aetiological influences of earlier era constructs on current state, free of confounding by indirect (often selection) effects. RESULTS: Our results indicate that psychological morbidity (particularly posttraumatic stress disorder) is largely influenced by combat and poor homecoming experiences, although pre-military characteristics do play some direct roles in symptomatology. Social dysfunction measures show smaller effects of the Vietnam War, which may be accounted for by an indirect association with Vietnam-related psychological morbidity. Some social measures show evidence of compensatory influences of combat, high combat leading to social dysfunction because of morbidity, but simultaneously being associated with healthier social disposition (possibly because of increased exservice activity). CONCLUSIONS: For Australian Vietnam veterans, combat-related and homecoming effects persist on a range of psychosocial endpoints 20-30 years after exposure. These effects are not explicable in terms of veterans pre-Vietnam characteristics.

Adolescent↗

PubMed1995

Methods for cell proliferation analysis by fluorescent image cytometry.

Methods were developed for multimodal microscopic image analysis in order to identify and analyze one cell type under various microscopic conditions. Our purpose was to quantify both total DNA content using propidium iodide (PI) stain and S-phase fraction using the bromodeoxyuridine (BrdUrd) incorporation technique in cell population subsets. The model chosen was plasma cells in bone marrow triply labelled with fluorescein isothiocyanate (FITC) for intracytoplasmic immunoglobulins, with amino-methylcoumarin-acetate (AMCA) for BrdUrd, and with PI for DNA. Image analysis included three phases. First, plasma cells were recognized on FITC images, and the centroid positions were stored. Second, plasma cell nuclei were geodesically reconstructed from these stored positions using PI images in which DNA content was measured, and the nuclear mask outlines were stored. Third, BrdUrd incorporation level of plasma cells was measured on AMCA images inside PI nuclei masks and stored. Image DNA vs. BrdUrd scatterplots were obtained for cells selected according to the expression of intracytoplasmic immunoglobulin. Thus, both ploidy and proliferation could be independently evaluated on a subset of the cellular population.

Animals↗

PubMed1995

Cdk1 is a marker of proliferation in human lymphoid cells.

To better understand the relationship between the proliferation of human lymphoid cells and the expression of cdk1, a catalytic subunit of the histone H1 kinase (H1K), we examined its mRNA and protein content in 3 B-cell lines: Ramos, Reh-6 and IARC 963. Cells were elutriated according to their position in the cell cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by Northern blot and immunoblot, respectively, as well as for H1K activity. Both mRNA and protein amounts and H1K activity varied according to cell cycle phase, the lowest values being observed in G1-enriched fractions. For comparison, elutriated fractions were also tested for the expression of cdk2 and cdk4 proteins. Both showed some variations among fractions, but they were less clear than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non-neoplastic tissues for proliferative activity (percentage of S and G2/M cells estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We found a significant correlation between the percentage of cells in S or S + G2/M phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA and protein levels.

Biomarkers↗

PubMed1995

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

PURPOSE: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible. The other biologic variables studied were related to tumor burden (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin) or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was found between LI and serum C-RP. LDH was the sole variable significantly correlated to C-RP (P < 0.01). Besides the biologic parameters used for the staging according to the Durie and Salmon classification, beta 2-M, albumin and LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001). LDH and C-RP showed no significant difference. Results were similar when patients with and without bone lesions were analyzed separately. Multivariate analysis ranked these variables as follows with respect to prognostic value: beta 2-M, LI, and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector of cell proliferation. We confirm its diagnostic and prognostic value.

Adult↗

PubMed1995

Post-transplant lymphoproliferative disorders with genetic abnormalities commonly found in malignant tumours.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of organ transplants. Impairment of the immune system by immunosuppressive drugs is the assumed cause of PTLD. The Epstein-Barr virus (EBV) is detected in most of the PTLD studied and is considered as the main aetiological agent. The clinical course of PTLD patients remains unpredictable, some lymphoproliferations regress after discontinuation of the immunosuppressive treatment, others behave as true malignant tumours. The mechanism by which a viro-induced lymphoproliferation evolves to an autonomous tumour remains unclear, and little is known about the genetic changes that occur during this process. We report two cases of fatal EBV-associated PTLD in heart transplant recipients. Both tumours were monoclonal and carried numerous chromosomal abnormalities, including a classic t(8;14)(q24;q32) with rearrangement of the MYC proto-oncogene. One tumour demonstrated an amplification of the proto-oncogene N-MYC. The EBNA2 gene was not expressed in tumoral cells, suggesting that the chromosomal abnormalities contributed the function of EBNA2 in these cells. The morphology of the tumours indicated that the cases presented here were not Burkitt's lymphomas. These findings provide some clues with regard to the genetic changes which lead to a B-cell malignancy in some transplant patients.

Adult↗

PubMed1995

Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.

Adult↗

PubMed1994

Choice of fixation and denaturation for the triple labelling of intra-cytoplasmic antigen, bromodeoxyuridine and DNA. Application to bone marrow plasma cells.

A triple staining method of intra-cytoplasmic antigen, bromodeoxyuridine (BrdU), and DNA for fluorescence image analysis is described. Several kinds of fixation and DNA denaturation methods were tested to obtain a technique suitable for heterogeneous tissues. The model chosen was the analysis of plasma cells in bone marrow. The fluorochromes used were fluorescein isothiocyanate (FITC) for intra-cytoplasmic antigens (light chain immunoglobulins), aminomethylcoumarin acetic acid (AMCA) for BrdU, and propidium iodide (PI) for DNA. The quality of the staining was analysed according to: (1) cell morphology with a good preservation of the chromatin structure, (2) intensity of light chains and of BrdU labelling, and (3) the quality of DNA staining judged from a DNA histogram. For most of the analysed tissues, fixation with methanol followed by 0.5% paraformaldehyde and denaturation by an NaOH concentration adapted to the tissue gave good results. However, in our model fixation by methanol, followed by methanol/acetic acid and denaturation of DNA by 0.03 N NaOH was the solely satisfactory technique. A good correlation (P < 0.001) was found with the plasma cell BrdU labelling index obtained with our reference immuno-enzymatic technique. Quantification of DNA content showed a satisfactory G1 peak coefficient of variation (CV) in diploid cells and a 4C to 2C ratio equal to 2. With this technique, the nuclear and cytoplasmic structures of both myeloid cells and plasma cells were well preserved, while their sensitivity to DNA denaturation was quite different.

Antigens↗

PubMed1994

Heterogeneity of neoplastic and reactive cell proliferation in non-Hodgkin's lymphomas linked to patient survival.

This study was undertaken to determine the characteristics of the proliferation of malignant and reactive cells in non-Hodgkin's lymphoma (NHL). Cell kinetics were studied in 76 previously untreated cases of NHL by flow cytometry after a double labeling of membrane antigen and DNA. Results were analyzed according to clinical and biologic characteristics of the patients. In B-cell NHL, percentages of B and T cells in S-phase were strongly linked (r = .82). The level of proliferation of malignant B cells and reactive T cells was significantly higher in aggressive lymphomas, compared with low grade, diffuse small cleaved cell NHL or reactive lymph nodes (P < .001). The percentages of malignant B cells in S-phase were lower when reactive T cells were more numerous (n = 59, r = -.264, P < .05), particularly in high-grade NHL (n = 16, r = -.78, P < .001). In the whole population of patients, survival was longer when the percentage of cells in S-phase (n1 = 38, n2 = 33) or S+G2 + mitosis (M) (n1 = 36, n2 = 35) was less than 3.2% and 7.25%, respectively (P < .005). When considering only B-cell NHL, survival was longer when the percentage of B cells in S-phase was less than 4.5% (n1 = 31, n2 = 28, P < .04). Among the slowly proliferative groups of lymphomas, this prognostic value was retained when S-phase value was less than 1% (n1 = 16, n2 = 13, P < .002). Furthermore, prognosis was better when the percentage of T cells in S-phase was less than 2.75% (n1 = 30, n2 = 29, P < .01) or when reactive CD4-positive T cells were more than 14.5% (n1 = 24, n2 = 24, P < .04). This result remained true in the group of highly proliferative lymphomas. These results illustrate the complexity of the interactions between malignant and reactive cells in NHL, with possible opposite effects on tumor cell growth.

Adolescent↗

PubMed1994

Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation.

Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p < 0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.

Acute Disease↗

PubMed1994

Fluorescence image analysis of plasma cells in monoclonal gammopathies.

The DNA content of plasma cells was estimated by fluorescence image analysis in monoclonal gammopathies. Image analysis provides the possibility of measuring the bone marrow plasma cell population separately from the other myeloid cells. Plasma cells were labeled, identified and then relocated for propidium iodide intensity measurements. Patients with DNA malignancy grade > 0.20 or with DNA index > 1.15 had a poorer survival rate than did patients with a low DNA malignancy grade or DNA index. DNA malignancy grade is based on the variance of DNA values around the normal diploid peak, as proposed by Böcking. Of all the biologic and clinical parameters investigated, the serum beta 2 microglobulin level was the most important prognostic factor for survival in the multivariate regression analysis, and the DNA entropy index provided the most significant additional information.

Aged↗

PubMed1993

Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.

The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL-1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD-1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over-expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)-associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13)-associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation.

Aged↗