PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Precursor Cell Lymphoblastic Leukemia-Lymphoma”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1992

Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s.

OBJECTIVE: To identify changes in practice and outcome of bone marrow transplants for leukemia in the 1980s. DESIGN: Comparison of key explanatory and outcome variables in five 2-year cohorts, from 1980 through 1981 to 1988 through 1989, using a large database of detailed clinical information. PATIENTS: Recipients (7788) of bone marrow transplants for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia reported to the International Bone Marrow Transplant Registry, Milwaukee, Wis, by 185 transplant teams worldwide. RESULTS: Linear increases occurred during the periods 1980 through 1981 to 1988 through 1989 as follows with 95% confidence intervals: (1) transplants for chronic myelogenous leukemia from 14% +/- 2% to 35% +/- 2%; (2) transplants from unrelated donors from 1% +/- 1% to 7% +/- 1%; (3) preparative regimens without radiation from 3% +/- 1% to 30% +/- 2%; and (4) use of methotrexate plus cyclosporine to prevent graft-vs-host disease from 2% +/- 1% to 55% +/- 2%. Among recipients of human lymphocyte antigen-identical sibling bone marrow, the 2-year probability of treatment-related mortality decreased by 6% to 22%. The probability of relapse decreased from 46% +/- 6% to 38% +/- 6% in intermediate leukemia but did not change appreciably in early or advanced leukemia. Probabilities of leukemia-free survival improved from 51% +/- 4% to 57% +/- 3% in early leukemia, from 28% +/- 4% to 36% +/- 5% in intermediate leukemia, and from 12% +/- 4% to 18% +/- 5% in advanced leukemia. A separate analysis of a homogenous population of patients indicated that improvements in outcome in the 1980s were due to improvements in transplant practice rather than improved patient selection. CONCLUSIONS: Modest increases in leukemia-free survival rates occurred after human lymphocyte antigen-identical sibling bone marrow transplants in the 1980s. Improvements were due primarily to reductions in treatment-related mortality with little or no change in relapse risk. More effective antileukemia strategies and continued reductions in treatment-related toxic effects are needed.

Adult↗
PubMed1992

DNA topoisomerase II immunostaining in human leukemia and rhabdomyosarcoma cell lines and their responses to topoisomerase II inhibitors.

DNA topoisomerase II is an enzyme that affects nuclear structure and function and is the target of a number of anticancer drugs in clinical use, including teniposide (VM-26). We have used our polyclonal antisera that recognize both the M(r) 170,000 and 180,000 forms of topoisomerase II to examine the nuclear distribution of topoisomerase II in cytospin preparations of drug-sensitive (CEM) and VM-26-resistant (CEM/VM-1 and CEM/VM-1-5) human leukemic lymphoblasts. We have also examined the nuclear distribution of topoisomerase II in monolayer cultures of a human rhabdomyosarcoma (Rh30) cell line. In the absence of drug, we observed a focal "patchy" staining of nuclear topoisomerase II in all cell lines, that was especially notable in the lymphoblastic cells. Treatment of CEM and Rh30 cells with VM-26 under conditions that increase the number of covalent topoisomerase II-DNA complexes increased both the intensity and the homogeneity of nuclear topoisomerase II staining in a subpopulation of cells; focal staining was less evident after treatment with drug. These responses were roughly proportional to the concentration of VM-26 used and required only brief (approximately 25-min) incubation with drug. We also found that treatment of CEM cells with 4'-(9-acridinylamino)methanesulfon-m-anisidide similarly increased the intensity and homogeneity of nuclear topoisomerase II immunostaining. In contrast, 4'-(9-acridinylamino)methanesulfon-o-anisidide and 1-beta-D-arabinofuranosylcytosine, agents that do not inhibit topoisomerase II, did not produce this effect. Finally, the VM-26-mediated alteration in topoisomerase II staining intensity and distribution was attenuated in proportion to the degree of VM-26 resistance in the CEM/VM-1 and CEM/VM-1-5 sublines. These results appear to be related to the ability of the drug to stabilize DNA-topoisomerase covalent ("cleavable") complexes in intact cells. Our findings indicate that anti-topoisomerase II drugs, such as VM-26, have profound effects on the ability to detect topoisomerase II in the nucleus and provide a novel way of examining drug-stabilized DNA topoisomerase II complexes in intact single tumor cells.

Cell Division↗
PubMed1992

Effect of cell proliferation on H-ferritin receptor expression in human T lymphoid (MOLT-4) cells.

We have previously demonstrated the presence of receptors specific for human recombinant H ferritin (HrHF) on human T lymphoid cells (MOLT-4), and changes in receptor number and binding affinity with growth and cell cycling have now been examined. Specific binding of HrHF was maximal in MOLT-4 cells harvested during exponential growth with the cells in the DNA synthesis phase of the cell cycle. Specific binding decreased progressively to the plateau phase of growth with the cells in the resting phase of the cell cycle. Scatchard analysis of the competitive binding data for HrHF demonstrated that this decrease in binding was associated with a reduction in receptor number, from 42,140 per cell to 10,306 per cell. Receptor binding affinity increased only minimally over this period, from 7.1 x 10(7) L/mol to 14.9 x 10(7) L/mol. These results indicate that growth- and cell cycle-induced changes in H-ferritin receptor expression are primarily associated with changes in receptor number rather than receptor binding affinity. The present study demonstrates that the expression of this receptor is associated with the proliferative status of the cell and suggests that the H-ferritin receptor may mediate the putative regulatory role of H-ferritin.

Cell Cycle↗
PubMed1992

Peroxidase-negative and myelomonocytic antigen-positive acute leukemia.

Between 1983-1988 bone marrow samples obtained from 195 peroxidase-negative leukemia patients were analyzed for their surface antigens. Thirteen of these patients (6.7%) had myelomonocytic-positive and lymphoid-negative antigens. These leukemic cells reacted with CD13 in eight patients, CD33 in seven, CD11 in six and CDw41 in two. In none of these patients did the leukemic cells react with CD1, CD2, CD3, CD4, CD5, CD8, CD10, CD19 or CD20. Leukemic cells from two patients were reactive with CD7. These leukemic cells demonstrated L2 morphology in 11 patients and L1 morphology in one patient. The leukemic cells from the final patient were diagnosed as those of leukemic transformation of myelodysplastic syndrome. Chromosomal abnormality was observed in approximately half of the patients examined (6/10). Cytochemical analysis revealed that the leukemic cells were negative for periodic acid Schiff stain but positive for acid phosphatase. The prognosis of these patients was markedly poor as compared to acute lymphocytic leukemia or typical peroxidase-positive nonlymphocytic leukemia. Complete remission was induced in only 30% of patients and duration of survival was short (4.7 months). This suggests that myelomonocytic antigen-positive peroxidase-negative acute leukemia is a distinct type of leukemia and may require more aggressive therapy to improve survival.

Acid Phosphatase↗
PubMed1992

Characterization of Philadelphia-chromosome-positive acute leukemia by clinical, immunocytochemical, and gene analysis.

Philadelphia chromosome (Ph') was detected at presentation in 10 out of 110 patients with acute lymphoblastic leukemia (ALL) and five of 168 patients with acute myelogenous leukemia (AML). Two other ALL patients who had studies at relapse were also included in the analyses. One of the 12 Ph'-positive (Ph+) ALL patients had simultaneous expression of myeloid-associated antigen on the leukemic blasts, while all the five AML patients coexpressed markers of lymphoid cells. Double labeling of the cells with myeloperoxidase and CD10 on three Ph+ AML cases showed that most leukemic blasts expressed either myeloperoxidase activity or CD10 but not both. Cross-lineage gene rearrangements of T-cell receptor (TCR) beta-chain gene were detected in three of the eight Ph+ ALL patients tested. All the four Ph+ AML cases studied showed immunoglobulin heavy chain gene rearrangements, and three of them also had simultaneous rearrangements of TCR beta-chain gene. The results revealed that Ph+ acute leukemia in this study belonged either to ALL or mixed lineage leukemia, and none was pure AML. This finding is contrary to that of acute blast crisis of chronic myelogenous leukemia in which the majority of patients had myeloid transformation. Rearrangements of bcr were detected in four of the 10 Ph+ ALL and three of the four Ph+ AML patients tested. No significant difference was noted in the clinical or hematologic manifestations among Ph+ leukemia with or without bcr rearrangements.

Adult↗
PubMed1992

Rearrangement and diversification of T-cell receptor delta genes in acute lymphoblastic leukemia.

The current study was designed to determine the nucleotide sequence of two distinct T-cell-receptor delta chain (TCR delta) rearrangements which account for 95% of all rearranged alleles in common non-T, non-B lymphoid precursor acute lymphoblastic leukemia (LP-ALL). The results presented demonstrate that TCR delta rearrangements in LP-ALL are incomplete, immature, and involve V delta 2 to D delta 3 or D delta 2 to D delta 3 joints. These rearrangements are found in most cases of ALL. These results are consistent with the hypothesis that these leukemias originate in multipotent lymphoid precursor cells. The remarkable diversity of the rearrangements detected by polymerase chain reaction, cloning and sequencing demonstrates the clonal specificity and potential for detection of leukemic residual disease. However, in some cases the number of nucleotide differences may not be sufficient for the discrimination of leukemic and non-leukemic cells carrying V delta 2-(D)-D delta 3 rearrangements. A novel inversional rearrangement was demonstrated in one leukemia. This novel inversional rearrangement potentially increases the degree of diversity of the junctional region which encodes the antigen binding domain of TCR delta.

Base Sequence↗
PubMed1992

[Acute lymphoblastic leukemia in children: which prognostic factors in 1992?].

Considerable advances were made during the Eighties in the treatment of acute lymphoblastic leukemia in children, using an intensive treatment regimen. The impact of numerous diagnostic variables on the prognosis has been modified; their re-evaluation as prognosis factors is necessary. Great importance is now attributed to the appreciation of the tumor burden, to the immunophenotype, and most importantly to cytogenetic data. This paper describes the prognosis factors currently used to define risk-group, and risk-adapted treatment regimen.

Child↗
PubMed1992

[Tumor necrosis factor alpha activity in peripheral blood in patients with acute leukemia: changes and clinical implications].

The production of tumor necrosis factor alpha (TNF alpha) of peripheral blood mononuclear cells was investigated in 58 patients with acute leukemia. The results showed that the production of TNF alpha was significantly lower in 41 of the 58 patients than that of normal controls. The TNF alpha activity levels from patients with acute monocytic leukemia and acute myelomonocytic leukemia were higher than those from patients with acute lymphoblastic leukemia and acute granulocytic leukemia (P < 0.05). The TNF alpha activity level changed in various courses of the disease and returned to normal during the period of complete remission. It was noted that patients with higher or normal TNF alpha levels had a higher complete remission rate than those with lower TNF alpha level (P < 0.01). These results indicated that determination of TNF alpha maybe helpful in observing changes of the disease and predicting prognosis.

Adolescent↗
PubMed1992

T cell recognition of Epstein-Barr virus associated lymphomas.

Epstein-Barr virus, a lymphotropic herpesvirus of humans, has potent B cell growth transforming activity yet persists in the lymphoid tissues of most individuals as a lifelong asymptomatic infection. Virus induced B cell growth transformation in vitro is associated with the expression of a limited set of viral genes encoding six nuclear antigens (EBNA 1, 2, 3A, 3B, 3C and LP) and two latent membrane proteins (LMP 1, 2). Healthy virus carriers possess strong EBV specific CTL memory that can be reactivated in vitro. Here, we summarize experiments in which the antigenic specificities of these HLA class I restricted memory CTL responses have been mapped in a range of individuals with different HLA backgrounds. Of the known EBV latent proteins, EBNA 3A, 3B and 3C are frequently the dominant targets for such responses, but examples of responses directed against epitopes of EBNA 2, EBNA-LP or the LMP have been identified; by contrast, CTL responses against epitopes of EBNA 1 have not been observed. Epstein-Barr virus is associated with at least three malignancies of lymphoid origin--immunoblastic lymphomas of the immunosuppressed, endemic Burkitt's lymphoma and a subset of Hodgkin's disease. The immunoblastic lymphomas express the complete spectrum of EBV coded latent proteins and a cellular phenotype similar to that of in vitro transformed B lymphoblastoid cell lines; accordingly, they remain sensitive to EBV specific CTL recognition. Endemic BL cells are not recognized by such CTL, and at least three consistent features of this tumour could contribute to immune escape: (a) allele specific downregulation of HLA class I antigen expression, (b) absence/low expression of cellular adhesion molecules and (c) restriction of EBV latent protein expression to EBNA 1 only. The relative importance of these three features of the BL cell phenotype with regard to sensitivity to CTL recognition is re-interpreted in the light of recent results. Finally, the pattern of virus latent protein expression in EBV positive Hodgkin's disease is described, and the possibility of EBV specific CTL control against this tumour is discussed.

Antigens, Viral↗
PubMed1992

Antibodies to human herpes virus-6 in patients with acute lymphocytic leukemia.

Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in children. To further investigate this association, we obtained sera from 50 patients with ALL and 50 age-sex matched controls. Antibodies to HHV-6 were determined using ELISA and indirect immunofluorescent antibody (IFA) tests. No significant difference between antibody titers in the cases and controls was observed. Since seroepidemiologic studies have demonstrated higher HHV-6 antibody titers in young children than in adults, this serologic study suggests that the previous association reported for HHV-6 and ALL was a result of the age of the population rather than a relationship between the virus and the disease.

Adolescent↗
PubMed1979

Complications of tumour overkill when associated with high dose methotrexate therapy.

Three patients, in whom tumour overkill by cytotoxic treatment, including high dose methotrexate with folinic acid rescue, resulted in the 'phosphate shower syndrome' (hyper-uricaemia, hyperkalaemia and hyperphosphataemia with hypocalcaemia and tetany, with metabolic acidosis and acute renal impairment) are described. Severe methotrexate toxicity occurred in two of these patients. High dose methotrexate would appear contra-indicated in situations where massive tumour lysis is possible.

Adolescent↗
PubMed2026

Case Report: Immune-driven clonal selection underlying lineage switch from B-Precursor acute lymphoblastic leukemia to acute myeloid leukemia following inotuzumab ozogamicin.

Lineage switch (LS), defined as a change in leukemic lineage during the disease course, is a rare but clinically significant event in acute leukemia and is typically associated with poor prognosis. Although LS has been increasingly reported following targeted immunotherapies, the clonal mechanisms underlying this phenomenon remain incompletely understood, particularly in cases without KMT2A rearrangement. We report a case of LS from B-precursor acute lymphoblastic leukemia (BCP-ALL) to acute myeloid leukemia (AML) following treatment with the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin. To elucidate the clonal architecture underlying LS, targeted next-generation sequencing was performed on bone marrow samples obtained at multiple time points throughout the disease course. Genomic analysis demonstrated that the lymphoid and myeloid disease phases shared ancestral genetic alterations but displayed distinct mutational profiles. At the time of LS, TP53 and SMC1A mutations newly emerged, whereas only a subset of mutations detected at ALL relapse was retained. These findings suggest that the AML phase most likely resulted from the selective expansion of a genetically distinct subclone derived from a common progenitor, rather than the direct transdifferentiation of the dominant ALL clone, consistent with immunotherapy-driven clonal selection. Longitudinal genomic profiling revealed stepwise clonal evolution during disease progression, supporting a model of immunotherapy-driven clonal selection leading to LS. This case provides molecular evidence suggesting that immune-targeted therapy can promote expansion of minor pre-existing subclones with alternative lineage potential within a common progenitor even in non-KMT2A-rearranged leukemia. Our findings highlight the importance of comprehensive genomic monitoring during immunotherapy to identify therapy-resistant subclones and better understand mechanisms of lineage plasticity in acute leukemia.

Humans↗
PubMedDate not supplied

The expression of the ras p21 oncoprotein in the bone marrow smears of children with acute leukemia.

Point mutations of the ras genes have been detected in various hematologic malignancies. This genetic event may either occur in all malignant cells or be acquired by different subclones, which however, cannot be demonstrated adequately by analyzing only DNA derived from patient specimens. The availability of the ras p21 monoclonal antibody (MoAb) Y 13259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. In this report the expression of the ras p21 oncoprotein in the bone marrow smears of 35 children with acute leukemia has been analyzed. The smears were treated with the MoAb Y 13259, biotinylated goat anti-rat IgG, streptavidin, peroxidase and stained with diaminobenzidine (DAB). The intensity of the staining was evaluated by two independent observers as negative or equivocal (-/+), moderate (+) or intense (++), by counting one thousand cells. Patients were also classified according to the percentage of the stained cells into four groups (0, I, II, III). It was found that 22/35 (63%) were (+) or (++) positive as follows: 11/21 (52%) with ALL CALLA (+), 2/2 ALL-B, 3/3 ALL-T and 6/9 AML. In Group 0 (none of the blasts was stained) were 13/35 (37%), as well as in Group I (1 to 25% of the blasts stained 1+ or 2+ positive), while in Group II (26 to 50% positive stained) 3/35 and in Group III (more than 51% stained) 6/35, all of which were AML (6/9). It is concluded that the immunohistochemical analysis of the ras p21 in blast cells of children with acute leukemia may demonstrate that ras gene expression in some subclones, the intensity and percentage of which may be of some clinical importance.

Acute Disease↗
PubMed1992

Enhanced insulin-receptor tyrosine kinase activity associated with chromosomal translocation (1;19) in a pre-B-cell leukemia line.

The gene for the insulin receptor has been assigned to chromosome 19 near the breakpoint of the translocation t(1;19) which occurs in 25% of pre-B-cell leukemias. Insulin receptors in a pre-B-cell leukemia cell line (ACV) with t(1;19) were found to have 2-fold higher affinity for insulin, 5-fold higher basal and insulin-stimulated beta sub-unit autophosphorylation, and 2-fold higher basal and 4-fold higher insulin-stimulated beta sub-unit kinase activity on the synthetic peptide poly(Glu,Tyr), compared to receptors in a B-cell line (ADD) with normal karyotype from the same patient. ACV cells had a novel 13-kb receptor mRNA species and expressed a DNA polymorphism localized to the tyrosine kinase domain of the receptor gene. These findings suggest that t(1;19) in the ACV cell may result in rearrangement of the insulin receptor gene and translation of a receptor with enhanced tyrosine kinase activity.

Blotting, Northern↗
PubMed2025

Cytogenetic and molecular characterization of an atypical ETP-ALL case with BCL2 dependency: therapeutic implications for Venetoclax use.

BACKGROUND: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, high-risk subtype of T-ALL characterized by distinctive immunophenotypic and genomic features. It is often associated with induction failure and frequent relapses. Despite recent advances in its molecular characterization, the prognosis remains dismal, and effective targeted therapies are limited. METHODS AND RESULTS: We report a pediatric, multi-refractory ETP-ALL case with novel cytogenetic alterations, including a 4q deletion and a t(16;18)(q24;q21) translocation. Molecular profiling revealed progressive activation of the BCL2 pathway and disruption of Th17-related immune markers. Ex vivo sensitivity assays performed at different disease stages demonstrated increasing BCL2 dependency. Based on these findings, venetoclax was administered on a compassionate-use basis, resulting in rapid hematologic recovery and a marked reduction in blast percentage. CONCLUSIONS: This case highlights the role of clonal evolution and immune deregulation in accompanying BCL2 addiction in relapsed ETP-ALL. Altogether, our findings underscore the therapeutic potential of venetoclax in refractory pediatric ETP-ALL cases with progressive BCL2 dependency.

Humans↗