Detection and treatment of molecular relapse in acute myeloid leukemia with RUNX1 (AML1), CBFB, or MLL gene translocations: Frequent quantitative monitoring of molecular markers in different compartments and correlation with WT1 gene expression

Doubek, Michael; Palásek, Ivo; Pospíšil, Zdeněk; Borský, Marek; Klabusay, Martin; Brychtová, Yvona; Jurček, Tomáš; Ježíšková, Ivana; Krejčí, Marta; Dvořáková, Dana; Mayer, Jiřı́

doi:10.1016/j.exphem.2009.03.004

Cited by 24 publications

(24 citation statements)

References 26 publications

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“…Molecular relapse was defined as the reappearance of the monitored fusion transcript or its 10-fold increase when detected repeatedly, together with normal BM morphology, immunophenotype, and cytogenetics, as has been recently described by our group (Doubek et al, 2009). Hematological relapse was defined based on standard hematological criteria.…”

Section: Dna Isolation and Chimerism Analysismentioning

confidence: 99%

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Horký

Mayer

Kablásková

et al. 2011

Int J Lab Hematology

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Section: Dna Isolation and Chimerism Analysismentioning

confidence: 99%

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Horký

Mayer

Kablásková

et al. 2011

Int J Lab Hematology

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“…MYC amplification in acute myeloid leukemia patients marks the state of the chemotherapy response [22]. The fusion gene type of CBFB is always related to Leukemia [23]. Based on the common origins of most of cancer diseases, the result suggests that the tight correlation among different cancer phenotypes could be used as an additional supervision in cancer biomarker discovery.…”

Section: Discussionmentioning

confidence: 96%

Seed-weighted random walks ranking method and its application to leukemia cancer biomarker prioritizations

Huan

Bai

et al. 2009

2009 IEEE International Conference on Bioinformatics and Biomedicine Workshop

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The identification of effective biomarkers for preventive intervention or targeted therapies will increase survival rate of cancer patients dramatically. However, the unclear molecular mechanism of carcinogenesis still blocks the discovery process of effective cancer biomarkers. Network-based analyses have been introduced into computational biomarker discovery for many years. The random walks ranking (RWR) algorithm is one of the most successful methods, which use known cancer susceptivity genes as seeds, and exploit global network topology to prioritize proteins in a protein-protein interaction (PPI) network. In this paper, we proposed a modified method -seed weighted RWR (SW-RWR) for prioritizing cancer biomarker candidates, which used the information of cancer phenotype association for assigning each seed gene a weighted value to guide RWR algorithm in a global human PPI network. From a case study in leukemia, SW-RWR outperformed a local network analysis in coverage and also showed better accuracy and sensitivity than the original RWR method. The result suggests that the tight correlation among different cancer phenotypes could play an important role in cancer biomarker discovery.

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“…33 In non-APL AML, a Czech group has published their results treating molecular relapses using anti-CD33, "5 ϩ 2"-like chemotherapy, donor lymphocyte infusion, or discontinuation of immunosuppression, showing that administration of preemptive therapy can often postpone HR but that HR will ultimately occur in a large majority of cases (10 of 13 relapses treated). 34 None of these studies entails a randomized comparison between action and no action on MR, and it must be admitted that no such studies are available to document the effect of preemptive action. However, a very stringently performed study by Rubnitz et al 35 has, however, shown encouraging results in childhood AML, where risk-adapted treatment according to MRD criteria resulted in improved outcome.…”

Section: Clinical Intervention Based On Mrd Results: the Critical Issuementioning

confidence: 99%

Towards individualized follow-up in adult acute myeloid leukemia in remission

Hokland

Ommen

2011

Blood

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An increasing body of data has demonstrated that the traditional concept of morphologic complete remission in acute myeloid leukemia, in which less than 5% myeloblasts is regarded as a sufficient response criterion, is not biologically sound. Fortunately, the quantitative reverse-transcribed polymerase chain reaction (RT-PCR) method seems to be a promising alternative because of its high degree of preclinical standardization and extreme sensitivity on the background of an accurate day-to-day estimate of sample quality. Widespread implementation of this has, however, to some extent been hampered by the lack of knowledge of how and when to measure minimal residual disease levels and, even more importantly, how to react preemptively on a molecular relapse defined by a PCR reversal. Thus, only few prospective studies have been published to date to clinically validate this assay. Here, we discuss outstanding issues in the clinical implementation of RT-PCR for fusion transcripts, mutated and overexpressed genes in acute myeloid leukemia patients in complete remission, and propose a set of guidelines, which can be used when designing prospective trials aimed at validating the use of RT-PCR as well as for following these patients based on mathematical models for disease recurrence recently developed in our laboratory. (Blood. 2011;117(9):2577-2584) IntroductionClassification of acute myeloid leukemia (AML) is now increasingly based on biologically highly relevant genetic abnormalities, such as the recurrent genetic abnormalities, including balanced translocations t, (8,21), inv(16)/t,(16,16) t(15;17), t(6,9) inv(3)/ t(3,3) t(1;22), other cytogenetic findings, or mutated genes (FLT3, NPM1 and CEBPA). 1 The reason that such a classification has superseded morphologic and immunophenotypic ones like the French-American-British is that they entail clear implications for prognosis as evidenced in several seminal papers, summarized in Schlenk et al. 2 Ideally, these advances in characterizing AML patients should result in a platform for risk-adapted treatment for the majority of patients. Although such an approach has been hinted in recent World Health Organization classifications of the disease, 1 it must be realized that these basic advances in our understanding of AML biology has only to a limited extent been accompanied by improved survival. This is because the majority of patients who obtain complete remission (CR) relapse from a state of "deep hematologic CR" depicted in Figure 1. 3 In this context, the term minimal residual disease (MRD) was developed to denote the source of relapse in those patients, in whom no detectable disease was present by standard diagnostic tests, but who did nonetheless experience a recurrence of the leukemic clone. 3 These observations in turn imply that the traditional hematologic relapse concept encompassing declining hematopoiesis and subsequent symptoms related to bone marrow failure need to be reevaluated and new terminologies defined. In Figure 2, we define these and will use these terms...

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Detection and treatment of molecular relapse in acute myeloid leukemia with RUNX1 (AML1), CBFB, or MLL gene translocations: Frequent quantitative monitoring of molecular markers in different compartments and correlation with WT1 gene expression

Cited by 24 publications

References 26 publications

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Seed-weighted random walks ranking method and its application to leukemia cancer biomarker prioritizations

Towards individualized follow-up in adult acute myeloid leukemia in remission

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