Predinsome therapy of acute childhood leukemia: Prognosis and duration of response in 330 treated patients

Wolff, James A.; Brubaker, Charles A.; Murphy, Michael; Pierce, Mila; Severo, Norman

doi:10.1016/s0022-3476(67)80052-0

Cited by 64 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 In a study of 271 murine lymphoid cell lines the glucocorticoid receptor was shown to be the primary target for development of glucocorticoid resistance. 4 Resistance to glucocorticoids is significantly increased in childhood ALL patients at relapse compared to diagnosis.…”

Section: Introductionmentioning

confidence: 99%

High level resistance to glucocorticoids, associated with a dysfunctional glucocorticoid receptor, in childhood acute lymphoblastic leukemia cells selected for methotrexate resistance

et al. 2001

View full text Add to dashboard Cite

The molecular basis for the clinical presentation of broad-range drug resistance in childhood ALL is poorly understood. In this study, high level cross-resistance to the glucocorticoid dexamethasone was encountered in a childhood ALL cell line selected for resistance to methotrexate (CEM MTX-R3). Compared with wild-type (WT) CEM cells, MTX-R3 cells had significantly fewer glucocorticoid binding sites, as well as reduced glucocorticoid receptor protein and mRNA levels. DNA sequencing and restriction fragment-length polymorphism (RFLP) analysis showed that WT cells expressed both a wild-type and a mutant (GR753F) glucocorticoid receptor allele, while MTX-R3 cells expressed only the GR753F allele. Therefore, the crossresistance of MTX-R3 cells to dexamethasone appeared due to loss of expression of the wild-type glucocorticoid receptor allele. In an effort to gain insight into the underlying basis for the development of cross-resistance to methotrexate and glucocorticoids, glucocorticoid receptor nuclear translocation experiments were carried out. Exposure of WT cells to either dexamethasone or the cytotoxic agents cytarabine and methotrexate caused translocation of the glucocorticoid receptor from the cytoplasm into the nucleus. These data indicate that exposure of childhood ALL cells to cytotoxic agents may result in ligand-independent glucocorticoid receptor activation which, in the context of the outgrowth of drug-resistant cells, could lead to the co-selection of glucocorticoid resistance. Leukemia (2001) 15, 929-935.

show abstract

Section: Introductionmentioning

confidence: 99%

High level resistance to glucocorticoids, associated with a dysfunctional glucocorticoid receptor, in childhood acute lymphoblastic leukemia cells selected for methotrexate resistance

et al. 2001

View full text Add to dashboard Cite

show abstract

“…The ability of glucocorticoid hormones to induce apoptosis in leukemia and lymphoma cells has been utilized by physicians for nearly a half-century (1,2). Today glucocorticoids are common components in many chemotherapeutic protocols for lymphoid malignancies, including multiple myeloma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma (3)(4)(5)(6).…”

mentioning

confidence: 99%

Microarray Analysis Uncovers the Induction of the Proapoptotic BH3-only Protein Bim in Multiple Models of Glucocorticoid-induced Apoptosis

Wang¹,

Malone²,

He³

et al. 2003

Journal of Biological Chemistry

198

223

View full text Add to dashboard Cite

Despite being one of the earliest recognized and most clinically relevant forms of apoptosis, little is known about the transcriptional events that mediate glucocorticoid-induced apoptosis. Therefore, we used oligonucleotide microarrays to identify the pattern of dexamethasone-induced changes in gene expression in two well characterized models of glucocorticoid-induced apoptosis, the murine lymphoma cell lines S49.A2 and WEHI7.2. Dexamethasone treatment induced a diverse set of gene changes that evolved over a 24-h period preceding the onset of cell death. These include previously reported changes in the expression of genes regulating prosurvival signals mediated by c-Myc and NFB. Unexpectedly, we discovered that glucocorticoid treatment increases expression of the gene encoding Bim, a BH3-only member of the Bcl-2 family that is capable of directly activating the apoptotic cascade. Induction of Bim was confirmed by immunoblotting not only in S49.A2 and WEHI7.2 cells but also in the human leukemia cell line CEM-C7 and in primary murine thymocytes. All three prototypical isoforms of Bim (Bim EL , Bim L , and Bim S ) were induced by dexamethasone. Because elevated expression of Bim initiates the execution phase of cell death, this report that Bim is induced by dexamethasone provides novel insight into the mechanism through which glucocorticoid-mediated changes in gene expression induce apoptosis in lymphoid cells.

show abstract

“…Most of the reported cases recovered spontaneously from the aplastic phase; prompt response to predni sone has also been described [1][2][3][4][5][6][7][8]. It is not clear whether the aplastic phase represents a true marrow failure preceding the development of ALL or the re mission of undiagnosed ALL.…”

Section: Discussionmentioning

confidence: 99%

“…In children typical aplastic anemia (AA) may pre cede the onset of acute lymphoblastic leukemia (ALL); the aplastic phase is transient and remission may be spontaneous or rapidly induced by corticoste roids [1][2][3][4][5][6][7][8]. This modality of presentation is observed in about 2-3% of pediatric ALL cases [8].…”

Section: Introductionmentioning

confidence: 99%

Adult Leukemia Developing after Aplastic Anemia: Report of 8 Cases

et al. 1988

View full text Add to dashboard Cite

481 cases of adult leukemia (115 acute lymphoblastic leukemia, ALL, and 366 acute nonlymphoid leukemia, ANLL) diagnosed at the Hematology Division of Pavia between 1976 and 1985 were reviewed to evaluate how many patients had an aplastic presentation. In 8 cases (1.6%) typical marrow hypoplasia preceded overt leukemia. At the leukemic transformation, the morphological and immunological findings were diagnostic for non-T non-B ALL in 2 cases, for ANLL in 5 cases (2 M1, 2 M2, 1 M5) and for Ph’-negative chronic granulocytic leukemia in 1 case. Median survival from the onset of leukemia was 5 months. In a certain proportion of cases aplastic anemia may be considered as a preleukemic state with a low propensity to develop into acute leukemia.

show abstract

Predinsome therapy of acute childhood leukemia: Prognosis and duration of response in 330 treated patients

Cited by 64 publications

References 3 publications

High level resistance to glucocorticoids, associated with a dysfunctional glucocorticoid receptor, in childhood acute lymphoblastic leukemia cells selected for methotrexate resistance

High level resistance to glucocorticoids, associated with a dysfunctional glucocorticoid receptor, in childhood acute lymphoblastic leukemia cells selected for methotrexate resistance

Microarray Analysis Uncovers the Induction of the Proapoptotic BH3-only Protein Bim in Multiple Models of Glucocorticoid-induced Apoptosis

Adult Leukemia Developing after Aplastic Anemia: Report of 8 Cases

Contact Info

Product

Resources

About