Prediction of risk of disease recurrence by genome-wide cDNA microarray analysis in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy

Zembutsu, Hitoshi; Yanada, Masamitsu; Hishida, Asahi; Katagiri, Toyomasa; Tsuruo, Takashi; Sugiura, Isamu; Jin, Tao; Usui, Noriko; Naoe, Tomoki; Nakamura, Yusuke; Ohno, Ryuzo

doi:10.3892/ijo.31.2.313

Cited by 7 publications

(9 citation statements)

References 46 publications

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“…Recently, Zembutsu et al [ 61 ] analyzed leukemia cells in bone marrows at diagnosis from patients in the JALSG Ph+ALL202 study by genome-wide cDNA microarray. Of 26 patients examined, 25 (96%) achieved CR, and after a median follow-up of 27 months, hematologic relapse occurred in 12.…”

Section: Prediction Of Relapse Risk By Genome-wide Cdna Microarray Anmentioning

confidence: 99%

“…The researchers categorized 25 CR patients into two groups: those who continued molecular CR for 1 year (group A) or those who molecularly relapsed within 1 year (group B). To extract genes that were differentially expressed between the two groups, they fi rst analyzed bone marrows of 19 patients (eight in group A and 11 in group B) by comparing expression levels of 27,648 genes, carried out frequent random permutation tests, and identifi ed 16 genes that were differently expressed between two groups [ 61 ].…”

Section: Prediction Of Relapse Risk By Genome-wide Cdna Microarray Anmentioning

confidence: 99%

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Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Ohno

2008

Curr Oncol Rep

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In the pre-imatinib era, treatment outcomes of adult patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) were dismal. Despite the use of intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), complete remission and overall survival rates were less than 70% and 20%, respectively. However, imatinib, in combination with conventional chemotherapy, has dramatically changed outcomes, producing approximately 95% complete remission and 50% overall survival with or without allogeneic HSCT. Current research is now focusing on how to prevent relapse. Improvement of postremission therapy is indispensable. Although allogeneic HSCT during first complete remission is still the first choice for feasible patients, post-HSCT imatinib therapy and imatinib plus chemotherapy combinations should also be studied. New BCR-ABL tyrosine kinase inhibitors are expected to improve outcomes in imatinib-resistant leukemia. Our hope is that, in the near future, Ph-positive ALL will become a leukemia in which allogeneic HSCT is offered only for relapsed or refractory cases.

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Section: Prediction Of Relapse Risk By Genome-wide Cdna Microarray Anmentioning

confidence: 99%

Section: Prediction Of Relapse Risk By Genome-wide Cdna Microarray Anmentioning

confidence: 99%

Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Ohno

2008

Curr Oncol Rep

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“…In some studies, imatinib was started during induction, as soon as Ph+ or BCR-ABL+ status was determined 26,[34][35][36] . In other studies, imatinib was started after remission was achieved, and the drug administered either continuously 25.27,30 or intermittently 21 .…”

Section: 22mentioning

confidence: 99%

Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

Couban¹,

Savoie²,

Mourad

et al. 2014

Current Oncology

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Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (TKIS) in the treatment of patients with Ph+ or BCR-ABL+ ALL has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of TKIS in patients with Ph+ ALL. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence.

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“…17,18 Briefly, gene expression profiling data from previous studies [7][8][9][10]19,20 comparing therapeutic response with various reagents in ALL patients were pooled and normalized. Relative expression levels were calculated, and associated with outcomes by analysis of variance (ANOVA).…”

Section: Selection Of Genes For Transcript Profilingmentioning

confidence: 99%

A pathway-based gene signature correlates with therapeutic response in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2010

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Biomarkers to predict response to therapy in adults with Philadelphia chromosome-positive (Ph þ ) acute lymphoblastic leukemia (ALL) are not yet established. In this study, we performed a meta-analysis of earlier genome-wide gene expression studies to identify pathway-based genes that are associated with therapeutic response. The predictive power of these genes was validated by transcript profiling in diagnostic bone marrow samples from Ph þ ALL patients using a quantitative real-time PCR array. Gene expression was correlated with cytogenetic and molecular characteristics, including presence of ABL1 mutations and IKZF1 deletion. A total of 43 de novo Ph þ ALL patients treated uniformly with tyrosine kinase inhibitors combined with chemotherapy were selected to validate 46 identified genes. A 9-gene signature was established to distinguish optimal responders from patients with persistent residual disease and early molecular recurrence. The signature was subsequently validated with 87% predictive accuracy in an independent validation set of patients. When initially optimal responders relapsed, their gene expression patterns also shifted. Optimal responders showed upregulation of genes involved in proliferation and apoptosis pathways, whereas poor responders had higher expression of genes that facilitate tumor cell survival in hypoxic conditions as well as development of drug resistance. This unique 9-gene signature may better enable stratification of patients to proper therapeutic regimens and provides new insights into mechanisms of Ph þ ALL response to therapy.

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Prediction of risk of disease recurrence by genome-wide cDNA microarray analysis in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy

Cited by 7 publications

References 46 publications

Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

A pathway-based gene signature correlates with therapeutic response in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

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