scholarly journals P53 protein overexpression in de novo acute myeloid leukemia patients with normal diploid karyotype correlates with FLT3 internal tandem duplication and worse relapse-free survival

2018 ◽  
Vol 93 (11) ◽  
pp. 1376-1383 ◽  
Author(s):  
Rita Assi ◽  
Hatice D. Gur ◽  
Sanam Loghavi ◽  
Sergej N. Konoplev ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
De Novo ◽  
P53 Protein ◽  
Protein Overexpression ◽  
Relapse Free Survival ◽  
Internal Tandem Duplication ◽  
Free Survival ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia

Blood ◽  
2009 ◽  
Vol 114 (14) ◽  
pp. 2993-3000 ◽  
Author(s):  
Ruoping Tang ◽  
Pierre Hirsch ◽  
Fanny Fava ◽  
Simona Lapusan ◽  
Christophe Marzac ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Young Patients ◽  
Disease Free Survival ◽  
Internal Tandem Duplication ◽  
Free Survival ◽  
Downstream Target ◽  
Disease Free ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Inhibitors of differentiation (Id) are a group of dominant inhibitors of basic helix-loop-helix transcriptional factors, which promote excessive proliferation, and also protect cells against drug-induced apoptosis in mammalians. Recently, Id1 has been identified as a common downstream target of several constitutively activated oncogenic tyrosine kinase, such as FLT3 internal tandem duplication, in leukemia cells. We analyzed Id1 expression as possible prognostic factor in 237 acute myeloid leukemia (AML) patients. High Id1 expression was associated with older age (P = .009) and with FLT3 internal tandem duplication (P = .003). However, 61% of the patients in the group of FLT3− AML were Id1+, suggesting that other tyrosine kinases are involved. In whole population, high Id1 expression independently predicted shorter disease-free survival (P = .05) and overall survival (P = .003). In young patients (age ≤ 60 years) with normal cytogenetics, Id1+ was, in multivariate analysis, associated with lower complete remission rates (P = .02), shorter disease-free survival (P = .02), and overall survival (P = .006). In conclusion, our data provide a new molecular marker for refining the risk classification of AML, especially in young patients with normal cytogenetic. Id1− patients with normal cytogenetic should be classified as favorable-risk leukemia. Id1, as a downstream target of constitutively activated tyrosine kinase, could be a suitable candidate for targeted therapy.

FLT3 Internal Tandem Duplication in Acute Myeloid Leukemia with Normal Karyotype

2007 ◽  
Vol 42 (3) ◽  
pp. 250 ◽  
Author(s):  
Sang-Ho Kim ◽  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Deog-Yeon Jo ◽  
Jong-Ho Won ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Normal Karyotype ◽  
Internal Tandem Duplication ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

scholarly journals Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia

2017 ◽  
Vol 35 (15) ◽  
pp. 1678-1685 ◽  
Author(s):  
Kenneth F. Bradstock ◽  
Emma Link ◽  
Juliana Di Iulio ◽  
Jeff Szer ◽  
Paula Marlton ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Gene Mutations ◽  
Severe Neutropenia ◽  
Consolidation Therapy ◽  
Internal Tandem Duplication ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.

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