Multilineage Dysplasia Confers Poor Prognosis to Patients with De Novo Acute Myeloid Leukemia with Intermediate-Risk Cytognetics and Wild-Type NPM1.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2551-2551
Author(s):  
Jose Tomas Navarro ◽  
Maria Rozman ◽  
Leonor Arenillas ◽  
Ana Aventin ◽  
Teresa Gimenez ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Leucocyte Count ◽  
Tandem Duplication ◽  
De Novo ◽  
Normal Karyotype ◽  
Intermediate Risk ◽  
Wild Type ◽  
Who Criteria ◽  
Multilineage Dysplasia

Abstract Abstract 2551 Background: The presence of multilineage dysplasia (MLD) is the hallmark to define acute myeloid leukemia (AML) with myelodysplasia-related changes. The recognition by the WHO classification of this category as a separate entity implies the presence of differential biological and clinical features. While this seems to be confirmed for patients with AML and MLD associated with high risk cytogenetic abnormalities, the prognostic significance of MLD in cases with intermediate risk karyotype is unclear. Recent studies have shown that MLD has no prognostic impact in patients with mutated NPM1, but the prognosis of patients with intermediate-risk cytogenetics and MLD harboring a wild-type configuration of NPM1 is uncertain. Objective: The aim of this study was to analyze the presence of MLD and its prognostic value in AML patients with intermediate risk cytogenetics (IR-AML) and wild-type NPM1. Patients and methods: One-hundred eighty-two patients diagnosed with de novo IR-AML and wild-type NPM1 treated with the same chemotherapy protocol (CETLAM-2003) were included (M/F:101/81; median age: 55.5, 18–73). Bone marrow aspirate smears performed at diagnosis were reviewed by a panel of expert cytologists, and the cases were categorized as having MLD by applying strictly the WHO criteria (Harris et al, WHO 2008, MLD-1). Additionally, cases with dysplasia in ≥50% of the cells in one cell line, and between 30% and 50% in another cell line, were classified as having significant dysplasia (MLD-2). Results: The degree of dysplasia was evaluable in 139 of the 182 cases, observing strictly WHO-defined multilineage dysplasia (MLD-1) in 45 (25%), significant dysplasia (MLD-2) in 17 additional patients (9%), and absence of MLD in 80 (44%). In 43 (30%) cases dysplasia could not be thoroughly quantified in all hematopoietic lines, mostly due to the lack of enough evaluable precursors in a context of massive blast infiltration. No major differences concerning main characteristics were observed between patients with or without MLD, including age, leucocyte count at presentation, degree of BM involvement, proportion of normal karyotype, and frequency of mutations of FLT3 (internal tandem duplication), CEBPA, and partial tandem duplication of MLL gene. Since the outcome of patients with MLD-2 was similar to that of patients with stringent WHO MLD, and markedly inferior to patients lacking MLD (table 1), these two groups were merged in a unique MLD group (MLD-1+MLD-2). Thus, MLD was associated with a lower probability to achieve complete remission (CR) after frontline induction chemotherapy (66% vs. 80%, p=0.033). In addition, patients with MLD showed a trend to an inferior overall survival (OS at 5 years: 39.2±5% vs. 22.9±8.1%, p=0.064). Of note, a multivariate analysis identified increasing age, higher leucocyte count at presentation, and presence of MLD (hazard ratio, 95% CI: 1.569,1.056–2.331; p=0.026) as the only variables associated with a shortened survival; this analysis also included presence of FLT3-ITD and cytogenetics (normal karyotype vs. other intermediate-risk abnormalities). Age was the only variable with independent prognostic value on leukemia-free survival in this cohort of patients, whereas MLD did not reach statistical significance. Interestingly, the outcome of patients with MLD-AML with a minimum CR duration of 3 months was significantly better after allogeneic stem cell transplantation in first CR compared to other post-remission treatments (5-year OS: 82±12% vs. 31±9%, p=0.006), suggesting that alloHSCT could partially overcome the adverse prognosis associated with this AML category. Conclusions: The presence of MLD confers adverse prognosis to patients with IR-AML and wild-type NPM1. Presence of significant dysplasia in two hematopoietic cell lines without fulfilling stringent WHO criteria was associated to an outcome similar to that of patients with WHO-defined criteria, an observation that leads to a wider interpretation of significant MLD in AML. These results have an important clinical relevance and should lead to the search of new genetic and epigenetic markers associated with MLD in this setting. This study has been partially supported by grant n° 03/0423 from Instituto de Salud Carlos III/FIS0. Disclosures: No relevant conflicts of interest to declare.

The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia patients with intermediate-risk cytogenetics is dependent on NPM1 mutational status

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6147-6148 ◽  
Author(s):  
Marina Díaz-Beyá ◽  
María Rozman ◽  
Marta Pratcorona ◽  
Montserrat Torrebadell ◽  
Mireia Camós ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
De Novo ◽  
Intermediate Risk ◽  
Multilineage Dysplasia ◽  
Mutational Status ◽  
Acute Myeloid

Importance of DNMT3A Gene mutations detection in Prognostic Analyses of Patients with Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5321-5321
Author(s):  
Ekaterina Petrova ◽  
Irina Martynkevich ◽  
Lyubov Polushkina ◽  
Lyudmila Martynenko ◽  
Marina Ivanova ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Molecular Markers ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Common Mutation ◽  
Intermediate Risk ◽  
Wild Type ◽  
Laboratory Parameters ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Objectives and background: Normal karyotype (NK) in AML patients accounts for nearly 45% of all cases and were assigned into intermediate risk group. The identification of new molecular markers in this group is the focus of most of researches. The application of the next-generation sequence techniques led to detect molecular markers with valuable prognostic significance. F.e., identification of DNMT3A mutations has gained the tremendous attention in recent times, because of its essential role in cell development, high frequency in AML patients and association of poor clinical outcome. Objects: to analyse character and frequency of DNMT3A mutations in AML patients; to study their associations with clinical and laboratory parameters and other molecular markers; to investigate their prognostic value. Methods: The screening of DNMT3A mutations was performed by the high-resolution melting curve analysis. Mutations in FLT3, CKIT and NPM1 were analysed by polymerase chain reaction and in NRAS by sequencing. Standard GTG-method was used for patients karyotyping. The investigation group included 98 AML patients. Missense mutations of DNMT3A exon 23 (R882) were identified in 16 (16,3%) de novo AML patients. The most common mutation in DNMT3A was R882H (n=9;56.3%), followed by R882C (n=6;37.5%), and R882S (n=1;6.2%). All but one patients (with mutation R882S) were heterozygous and retained a wild-type allele. Patients with isolated DNMT3A mutations were seen in 3 cases; 3 pts with R882C had also mutations in NRAS; 3 pts had DNMT3Amut/FLT3-ITDmut; 1 pt - DNMT3Amut/FLT3-ITDmut/ FLT3-TKDmut; 4 pts - DNMT3Amut/FLT3-ITDmut/ NPM1mut and 3 pts - DNMT3Amut/ NPM1mut. Results: Patients who harbored a mutation in DNMT3A had higher white blood cells count (p=0.039) at diagnosis and more frequently belonged to FAB group M4 (p=0.033), as compared with DNMT3A wild-type. Of the 16 patients who had AML with DNMT3A mutation, 13 (26.5%) had tumors with normal cytogenetic profiles (of a total of 49 cytogenetically normal samples) (p=0.006). There was no statistical correlation with other parameters, including sex, age, hemoglobin, and platelet count between patients with and without DNMT3A mutations (p>0.05). DNTM3A mutations were significantly more prevalent in NPM1 positive cases when compared to NPM1 wild type cases (p=0.000). DNTM3A mutations were also more dominant in FLT3-ITD positive pts than wild type (p=0.000). In contrast, DNMT3A mutations were not observed in cases with CKIT mutations indicating that these mutations can be mutually exclusive in nature. There was a statistical significance between overall survival (OS) of NK-AML pts with DNMT3A mutations and DNMT3Awt (p=0.032). Figure 1 Figure 1. Conclusions: AML with DNMT3A mutations represent the group, homogeneous on a number of clinical and laboratory parameters. DNMT3A mutations are highly recurrent in patients with de novo AML with an intermediate-risk cytogenetic profile. FLT3-ITD and NPM1 mutations appear as a major significant coexisting genetic mutations in DNMT3Amut pts. The presence of DNMT3A mutations can be considered as independent adverse prognostic factor for OS, suggesting that testing of DNMT3A mutations can help further improve risk stratification in NK-AML. References: Ley T.J., Ding L., Walter M.J., McLellan M.D. et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010;363:2424-2433. Disclosures No relevant conflicts of interest to declare.

scholarly journals Translocation (6;15)(q12;q15): A Novel Mutation in a Patient with Therapy-Related Myelodysplastic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Saba F. Ali ◽  
Rebecca J. Sonu ◽  
Denis M. Dwyre ◽  
Brian A. Jonas ◽  
Hooman H. Rashidi
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Value ◽  
De Novo ◽  
Novel Mutation ◽  
Normal Karyotype ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Response To Treatment ◽  
Unique Case ◽  
Autologous Bone Marrow Transplant

Most myelodysplastic syndromes (MDS) present with loss or gain of chromosomal material and less commonly show translocations as a sole abnormality. In addition, certain translocations are more commonly seen in MDS than others, but to our knowledge, the presence of t(6;15) has not been reported in MDS, specifically therapy-related MDS (t-MDS) cases. Patients with t-MDS, a group of heterogeneous stem cell related disorders resulting as a latent complication of cytotoxic and/or radiation therapy, generally tend to have a poorer prognosis thande novoMDS. We present a unique case of a patient who initially presented with acute myeloid leukemia (AML) with a normal karyotype and FLT3-ITD and NPM1 mutations. The patient was successfully treated with chemotherapy and an autologous bone marrow transplant but subsequently developed a new FLT3-ITD negative t-MDS with a unique translocation, t(6;15)(q12;q15), three years after transplant. To our knowledge, this unique sole translocation has never been reported in MDS or t-MDS and given her successful response to treatment and remission, presence of this translocation may have some prognostic value.

scholarly journals Acute Myeloid Leukemia Patients with an Undefined Genetic Profile at Diagnosis: Clinical and Prognostic Aspects

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5326-5326
Author(s):  
Marco Mancini ◽  
Teresa Ceglie ◽  
Saveria Capria ◽  
Anna Maria Testi ◽  
Roberto Latagliata ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Normal Karyotype ◽  
Risk Profile ◽  
Genetic Profile ◽  
Intermediate Risk ◽  
Wild Type ◽  
Molecular Analyses ◽  
Risk Patients

Abstract Conventional cytogenetics and molecular analyses allow to stratify acute myeloid leukemia (AML) patients into subgroups with different clinical and prognostic relevance. AMLs with unsuccessful cytogenetics and no known recurrent mutations are a subgroup of cases for which information on possible underlying genetic lesions of the leukemic cells is lacking and with a poorly defined outcome. Previous studies have quantified the rate of unsuccessful karyotyping in approximately 10% of the analyzed AML samples and it is conceivable that if cases with molecular rearrangements were to be included this figure could be lower. With the aim of investigating the prevalence and impact of cases with an undefined genetic profile (UGP), we studied 437 AML patients - 228 males and 209 females, with a median age of 50 years (range 1-81) - treated on successive intensive chemotherapy protocols at our Institution. Conventional cytogenetic and molecular analyses - RUNX1-RUNX1T1, CBFB-MY11, DEK-NUP214, FLT3-ITD, NPM1, BCR-ABL, MLL-PTD - were performed at diagnosis. According to the genetic alterations, patients were comprehensively stratified into three subgroups: a favorable risk group - t(8;21) RUNX1-RUNX1T1, inv(16) CBFB-MY11, normal karyotype with mutated NPM1 without FLT3-ITD - with a 5-year overall survival (OS) of 65%, an intermediate risk group - normal karyotype with mutated or wild type NPM1 and FLT3 ITD or wild-type NPM1 without FLT3-ITD, t(9;11)(p22;q23), cytogenetic abnormalities not classified as favorable or adverse - with a 5-year OS of 27% and an unfavorable risk group - inv(3)(q21q26) or t(3;3)(q21;q26), t(6;9)(p23;q34), DEK-NUP214, t(v;11)(v;q23), -5 or del(5q), -7, complex karyotype - with a 5-year OS of 11%. Thirty-three patients (7.5%) were identified as having an UGP and their baseline characteristics, as well as clinical outcome, were compared to those of patients with defined molecular and cytogenetic features. Patients with an UGP were older at the onset of the disease than those with a delineated genetic profile (median 55 vs 49 years). In addition, the proportion of UGP cases increased with age, being 3% in patients <20 years, 6% in patients between 20 and 50, and 9.5% in patients >50 years. The complete remission (CR) rate for UGP patients (69.6%) was similar to that of intermediate risk patients (71.1%), but inferior to that of patients with a favorable risk profile (90.5%) (p=0.0046) and better than that of unfavorable genetic risk patients (63.7%). After adjusting for age, gender, WBC and platelet count, Hb, marrow blast percentage at diagnosis and treatment, UGP remained an independent factor for lower CR rate with respect to patients with a favorable genetic risk profile. The frequency of relapse was significantly higher in patients with UGP compared to the favorable risk group (60.8% vs 32%) (p=0.011). In multivariate analysis, the 5-year OS of patients with UGP was significantly worse than that of patients with a favorable genetic risk profile (p<0001) and similar to that of the intermediate genetic risk subgroup. Our study documents that, despite progress in the detection of genetic lesions, patients with an UGP - having a failed karyotype and without known molecular markers - still represent an important subgroup in AML. An UGP occurs more frequently with increasing age and is associated with a worse outcome compared to patients with a favorable genetic risk profile and with a prognostic likelihood similar to that of intermediate risk AML patients. Disclosures No relevant conflicts of interest to declare.

Gene Expression Profiling of Acute Myeloid Leukemia with Multilineage Dysplasia (AML-MD) Reveals a Biological Diversity Related to Underlying Cytogenetics but Also Identifies a Distinctive Profile in Normal Karyotype AML-MD.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2244-2244
Author(s):  
María Rozman ◽  
Susana G. Kalko ◽  
Jordi Esteve ◽  
Mireia Camós ◽  
Josep-Lluís Aguilar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Intermediate Risk ◽  
Transcriptional Signature ◽  
Multilineage Dysplasia ◽  
Unsupervised Analysis ◽  
Acute Myeloid

Abstract Acute myeloid leukemia with multilineage dysplasia (AML-MD) is recognized as a major AML category in the WHO classification, closely related to myelodysplasia and associated with poor prognosis. The biological background of this entity, however, has not been extensively assessed. In this context, we analyzed the gene expression profile in a series of patients with AML-MD from our institution. First, the transcriptional signature of diagnostic samples from 19 patients with AML-MD (age: 71, 30–93; 8M/11F) was analyzed, including 11 cases of intermediate-risk cytogenetics and 8 adverse karyotype samples. In a second step, we selected from the previous analysis those AML-MD patients with normal karyotype (NK AML-MD, n=8) and compared their genomic profile with 11 additional samples corresponding to normal karyotype AML without underlying multilineage dysplasia (NK AML). Overall gene expression was examined with oligonucleotide HGU133 Plus 2.0 arrays (Affymetrix), and gene expression measures were normalized using RMA methodology from the Affy package (Bioconductor project). Unsupervised two-dimensional cluster analysis of highly variable genes was performed with the dChip v1.3 software. In addition, supervised analysis to identify genes with significant differential expression was done with the Limma package (Bioconductor), which employs Bayesian statistics adjusted for multiple testing. Unsupervised analysis among AML-MD patients identified two major groups, mainly clustered according to cytogenetics: Group 1 (n=10) contained 9 patients with intermediate-risk cytogenetics whereas Group 2 (n=9) showed predominance of high-risk karyotype (78%; p=0.006). Supervised analysis allowed the identification of a cluster of 92 genes differentially expressed according to cytogenetics category, such as several ribosomal constituents and genes involved in translation (RPS20, EIF3S3, LOC400055), which were overexpressed in intermediate-risk AML-MD, or genes involved in the immune response (FCGR3A-3B, IL1R2, PLXNC1, FCAR, CLEC4D-4E, TNFRSF10C, C5R1), found to be highly expressed in AML-MD with high-risk cytogenetics. In a further analysis, gene expression profiling of NK AML-MD was compared to NK AML. Interestingly, unsupervised analysis revealed a clear distinction between both subgroups, with 1861 genes differentially expressed. Moreover, a subset of 34 genes, selected according to a high index of variable expression (log fold change>1.0), showed a characteristic pattern in normal karyotype AML-MD. Among these, transcription factor TAL1, RNA-binding protein MSI2, and erythrocyte membrane protein RHAG were found to be overexpressed in NK AML-MD, while other genes such as RASSF4 and PIK3CD, involved in Ras signaling, or the transcription factor CEBPD were significantly underexpressed in this AML category. In conclusion, analysis of gene expression profile of AML-MD supports the biological heterogeneity of this AML category, partially associated with underlying cytogenetic abnormalities. Moreover, the striking distinctive profile observed in NK AML-MD suggests that multilineage dysplasia is associated to a specific transcriptional signature, distinguishable from normal cytogenetics AML lacking dysplastic features.

Incidence and Prognostic Value of FLT-3 and NPM1 Genes Abnormalities in Acute Myeloid Leukemia in the Côte D’or Population, France

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4873-4873
Author(s):  
Marc Maynadié ◽  
Martine Courtois ◽  
Morgane Mounier ◽  
Ines Janoray-Manivet ◽  
Ingrid Lafon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
De Novo ◽  
Relative Survival ◽  
Normal Karyotype ◽  
Npm1 Mutation ◽  
Clinical Series ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Context: In acute myeloid leukemia (AML), the recently described FLT-3 and NPM1 genes abnormalities were found to have a prognostic value in AML with normal karyotype and a specific therapeutic strategy was proposed according to these abnormalities. We look for the incidence and prognostic value of these abnormalities in cases diagnosed on a well defined population. Material and Methods: AML diagnosed according to WHO classification between 01/01/2001 and 31/12/2006 in the population of the Côte d’Or department, were included. Karyotype analyses were performed in 81% of the cases. The FLT3 D835 mutation, the FLT3 internal duplication (ITD) and the NPM1 mutation were systematically studied on the biological material of the diagnosis cryopreserved in the Ferdinand Cabanne Biobank of Burgundy, by PCR and DNA sequencing techniques. The vital status of the patients was update on 31/10/2007. The relative survival was calculated with the STATA (V9) software. Results: 100 de novo AML and 47 secondary AML (sAML) were registered (72 females and 75 males). The world standardized incidence rate was 2.4 in men and 1.5 in women for de novo AML instead of what it was respectively of 1.1 and 0.6 in sAML. The urban predominance was present in both type of AML. The karyotype was normal in 38% (45/119) of cases (35% of de novo AML and 21% of sAML). It was abnormal in 62% of cases (74/119)(51% of de novo AML and 49% of sAML). Molecular analyses were performed in 78 de novo AML and in 24 sAML. FLT3 ITD was present in 19% (15/78) de novo AMl and in any sAML. The FLT3 D835 mutation was present in 6.5% of de novo AML and in 8% of sAML. NPM1 was mutated respectively in 26% and 4% of the cases. There was a significantly higher WBC count and proportion of blast cells in peripheral blood in FLT3 ITD cases. Overall and relative survivals of FLT3 ITD cases were decreased compared to FLT3 wild type cases. No difference according to NPM1 status was found. Conclusions: These data confirm the bad prognostic value of FLT3 ITD status in AML observed in clinical series. Furthermore their particular interest lies in the fact that they are the first molecular data in AML produced on a population-based series indicating the feasibility of such epidemiological studies.

FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication and the Patterns of Its Gene Sequence in 207 Chinese Patients With De Novo Acute Myeloid Leukemia

2012 ◽  
Vol 136 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Ling Zhong ◽  
Yong Qian Jia ◽  
Wen Tong Meng ◽  
Xun Ni
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
De Novo ◽  
Chinese Patients ◽  
Wild Type ◽  
Internal Tandem Duplication ◽  
Tandem Duplications ◽  
Acute Myeloid

Context.—Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML). Objective.—To study the patterns of FLT3-ITD in Chinese patients with AML. Design.—A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives. Results.—A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML. Conclusion.—Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.

scholarly journals AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia

Blood ◽  
2014 ◽  
Vol 123 (6) ◽  
pp. 905-913 ◽  
Author(s):  
Erika K. Keeton ◽  
Kristen McEachern ◽  
Keith S. Dillman ◽  
Sangeetha Palakurthi ◽  
Yichen Cao ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Kinase Inhibitor ◽  
Wild Type ◽  
Internal Tandem Duplication ◽  
Rna Translation ◽  
Key Points ◽  
Messenger Rna Translation ◽  
Flt3 Internal Tandem Duplication

Key Points AZD1208 is a selective pan-Pim kinase inhibitor with efficacy in AML cells, xenografts, and Flt3-internal tandem duplication or Flt3 wild-type patient samples. AML cell growth inhibition is associated with suppression of p70S6K, 4EBP1 phosphorylation, and messenger RNA translation.

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