Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse

Garson, O. Margaret; Hagemeijer, A.; Sakurai, Masaki; Reeves, Brian; Swansbury, G. J.; Williams, G. J.; Arthur, DC; Berger, Roland; Chapelle, Albert de la; Dewald, GW; Mitelman, Felix; Berghe, Herman Van den; Lawler, Sylvia D.; Rowley, J.D.

doi:10.1016/0165-4608(89)90024-1

Cited by 62 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the other three reports, 168, 103 and 60 patients, respectively, were analyzed at both time points. [27][28][29] Changes were reported in 52%, 61% and 28%, respectively, which is in the range of the 38% observed in the current series. Changes occurred in patients with initially normal karyotypes in 30%, 51% and 25% (current series: 36%) and in patients with initially aberrant karyotypes in 67%, 68% and 31% (current series: 39%).…”

Section: Figurementioning

confidence: 90%

See 1 more Smart Citation

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy

et al. 2002

View full text Add to dashboard Cite

The instability of the karyotype may play a role in the development of refractoriness of acute myeloid leukemia (AML) to antileukemic therapy. Therefore, in the current study cytogenetic analyses were performed in 117 patients with AML both at diagnosis and at relapse. Changes in karyotype were observed in 38% (36% of initially normal karyotypes, 39% of initially aberrant karyotypes). An evolution of karyotype, ie the acquisition of further aberrations in addition to those present at diagnosis, occurred more frequently in patients with unfavorable karyotypes at diagnosis as compared to all others (60% vs 32%, P = 0.0095). The duration from initial diagnosis to relapse was significantly shorter in cases with an evolution of the aberrant karyotype as compared to cases with no changes in the aberrant karyotype between diagnosis and relapse or with solely regression of aberrations at relapse (9.2 ± 4.4 vs 14.0 ± 8.5 months, P = 0.0081). In an additional analysis, another cohort of 120 patients with refractory and relapsed AML who were treated uniformly within the respective trial of the German AML Cooperative Group was analyzed cytogenetically at diagnosis and at relapse to further prove the prognostic impact of karyotype aberrations at relapse. Karyotypes were prognostically favorable, intermediate, unfavorable and not available in 8%, 50%, 17% and 25% at diagnosis and in 8%, 49%, 21% and 22% at relapse, respectively. Karyotype aberrations at diagnosis had no impact on response to therapy (P = 0.32) but influenced survival and event-free survival significantly (P = 0.03 and P = 0.02). In contrast, karyotype aberrations at relapse strongly influenced response to therapy (P = 0.05), survival (P = 0.01), and event-free survival (P = 0.002). These data suggest that the instability of the karyotype between diagnosis and relapse and thus karyotype aberrations at relapse in particular contribute to the refractoriness of AML to anti-leukemic therapy.

show abstract

Section: Figurementioning

confidence: 90%

“…Also in two of the reports, complex aberrant karyotypes appeared to be particularly instable. 28,29 Contrasting patients with an evolution of karyotype, cases with aberrations independent on the initially diagnosed karyotype seem to have secondary or therapy-related AML.…”

Section: Figurementioning

confidence: 99%

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Further patients should be evaluated to add to the current data and also to clarify the role of chromosome abnormalities determined directly prior to salvage therapy which are different to the initial karyotype in about 60% of cases. 43 The results of these further analyses should be the basis for further trials that analyze in a randomized fashion different treatment strategies in the respective subgroups of patients. In addition, the negative results of the current analyses should be kept in mind, eg, the lack of influence of the application of high-dose AraC during first-line treatment on the outcome following S-HAM salvage therapy.…”

Section: Figurementioning

confidence: 99%

Multivariate analysis of prognostic factors in patients with refractory and relapsed acute myeloid leukemia undergoing sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy: relevance of cytogenetic abnormalities

et al. 2000

View full text Add to dashboard Cite

To improve the basis for the stratification of patients with refractory and relapsed acute myeloid leukemia (AML) univariate and multivariate analyses of prognostic factors were performed in 254 patients (median age 50 years, range 18-74) undergoing S-HAM salvage chemotherapy during two consecutive prospective trials of the German AML Cooperative Group. In a multivariate analysis, duration of the first complete remission (CR) was the only factor associated with time to treatment failure (P = 0.0223). Disease-free survival was influenced by a short duration of the first CR of less than 6 months (P = 0.0001), WBC (P = 0.0018), blast count (P = 0.0037), and neutrophil count (P = 0.0119). The achievement of CR was related to the hemoglobin level only (P = 0.0457), the early death rate was related to age only (P = 0.0109), and survival was related to the bilirubin level only (P = 0.0166). In the subgroup of 104 patients in whom additional karyotype analyses were performed prior to first-line therapy unfavorable chromosome abnormalities were associated with a lower CR rate (univariate analysis, P = 0.0342; CR 24% vs 53%) and were the only factor related to survival. These analyses warrant the further evaluation of the impact of cytogenetic abnormalities on the outcome of patients with advanced AML in order to improve the characterization according to duration of first CR and to WBC of distinct subgroups of patients with differing prognoses as a basis for stratification in future trials. Leukemia (2000) 14, 226-231.

show abstract

“…Common alterations in gene expression in relapsed AML PB Staber et al phenotypic differences described so far do not show consistent changes when analysed in a larger set of leukemic cases (Borella et al, 1979;Pui et al, 1986;Garson et al, 1989;Estey et al, 1995;Nakano et al, 1999;Baer et al, 2001;Hur et al, 2001). Data provided by our study using large-scale gene expression profiling add a subset of 58 genes commonly deregulated in AML REL, representing alterations, which might be characteristic for the development of recurrence.…”

Section: G-csf) Cr Indicates Complete Remission and Is Given In Monthsmentioning

confidence: 92%

“…Numerous reports have focused on these differences, as they can play an important role in treatment strategies. At relapse, over half of patients demonstrate karyotypic changes in the leukemic blasts, either towards more or less complexity or even reversion to a normal karyotype (Garson et al, 1989;Estey et al, 1995;Hur et al, 2001). Acquisition and/or loss of mutations are frequent , and immunophenotypic characteristics of blasts are often altered at the time of disease recurrence (Borella et al, 1979;Pui et al, 1986;Baer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia

Staber¹,

Linkesch²,

Zauner³

et al. 2004

Oncogene

View full text Add to dashboard Cite

Recurrent disease following high-dose chemotherapy is a major problem in patients with acute myeloid leukemia (AML). To identify its characteristics, we performed expression profiling in blasts from untreated AML and relapse, using a specific cDNA microarray comprising 4128 genes generated by cDNA subtraction supplemented with cancer-associated genes. Expression analysis of 18 AML bone marrow specimens showed that recurrent AML is commonly associated with the mRNA expression changes in a set of 58 genes. Increased cellular proliferation was indicated by the overexpression of the transferrin receptor, proliferating cell nuclear antigen, and G1 cyclins. An immunohistochemical study for Ki-67-positive blasts in 18 paired bone marrow biopsy samples confirmed a highly significant (Po0.0001) increase in the proliferation fraction at relapse. In addition, we found enhanced activation of the RAF/MEK/ERK cascade as mRNAs of MKP-1, c-jun, c-fos, and egr-1 were significantly increased at relapse. Immunohistochemistry and immunoblotting analyses for biphosphorylated ERK1/2 protein provide additional evidence for enhanced activation of the RAF/MEK/ERK pathway. The degree of increase is significantly correlated with the increased proliferation. Furthermore, the genes identified provide a rationale for further studies on predictive diagnosis and therapeutic intervention.

show abstract

Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse

Cited by 62 publications

References 0 publications

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy

Multivariate analysis of prognostic factors in patients with refractory and relapsed acute myeloid leukemia undergoing sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy: relevance of cytogenetic abnormalities

Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia

Contact Info

Product

Resources

About