scholarly journals Two novel CEBPA mutations in a Turkish patient with acute myeloid leukemia

2020 ◽  
Vol 23 (2) ◽  
pp. 99-102
Author(s):  
PE Tokgun ◽  
MT Alay ◽  
S Atli Tekin ◽  
N Güler ◽  
O Tokgun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Frameshift Mutation ◽  
Gene Mutations ◽  
Leukemic Cells ◽  
Laboratory Examination ◽  
Histological Changes ◽  
Turkish Patient ◽  
Cebpa Mutations ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) was first categorized in 1976 by French, American and British researchers, and divided into eight subgroups (M0 to M7), depending on the cytochemical or histological changes in the leukemic cells. The gene mutations of FLT3-ITD, CEBPA and NPM1 are the most common that cooperate together in the prognosis of AML. The CEBPA gene that is a hematopoietic transcription factor, is located on chromosome 19q13.11, and its prevalence is between 5.0 and 14.0% in AML. The patient was referred to our clinic suffering from menorrhagia, unplanned weight loss in a month and low platelet levels, and was diagnosed with AML on clinical and laboratory examination. Here, we report a patient carrying two novel pathogenic mutations that create a frameshift mutation on the CEBPA gene, c.940_941insCCGTCG TGGAGACGA CGAAGG and c.221_222delAC by Sanger sequencing methodology.

scholarly journals Nanopore Targeted Sequencing for Rapid Gene Mutations Detection in Acute Myeloid Leukemia

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1026 ◽  
Author(s):  
Cumbo ◽  
Minervini ◽  
Orsini ◽  
Anelli ◽  
Zagaria ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Cost ◽  
Gene Mutations ◽  
Predictive Biomarkers ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cebpa Mutations ◽  
Targeted Gene Sequencing ◽  
Acute Myeloid

Acute myeloid leukemia (AML) clinical settings cannot do without molecular testing to confirm or rule out predictive biomarkers for prognostic stratification, in order to initiate or withhold targeted therapy. Next generation sequencing offers the advantage of the simultaneous investigation of numerous genes, but these methods remain expensive and time consuming. In this context, we present a nanopore-based assay for rapid (24 h) sequencing of six genes (NPM1, FLT3, CEBPA, TP53, IDH1 and IDH2) that are recurrently mutated in AML. The study included 22 AML patients at diagnosis; all data were compared with the results of S5 sequencing, and discordant variants were validated by Sanger sequencing. Nanopore approach showed substantial advantages in terms of speed and low cost. Furthermore, the ability to generate long reads allows a more accurate detection of longer FLT3 internal tandem duplications and phasing double CEBPA mutations. In conclusion, we propose a cheap, rapid workflow that can potentially enable all basic molecular biology laboratories to perform detailed targeted gene sequencing analysis in AML patients, in order to define their prognosis and the appropriate treatment.

Detection of Nucleophosmin Gene Mutations in Plasma from Patients with Acute Myeloid Leukemia: Clinical Significance and Implications.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2855-2855
Author(s):  
Wanlong Ma ◽  
Xi Zhang ◽  
Iman Jilani ◽  
Farhad Ravandi ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Leukemic Cells ◽  
Striking Difference ◽  
Plasma Dna ◽  
Npm1 Mutation ◽  
Acute Myeloid

Abstract Nucleotides insertion in the nucleophosphamin (NPM1) gene has been reported in about one third of patients with acute myeloid leukemia (AML). Multiple studies showed that the presence of NPM1 mutations associated with better outcome in patients with AML. Studies reported to date have analyzed leukemic cells obtained from bone marrow or peripheral blood. We tested for mutations in the NPM1 gene using peripheral blood plasma and compared results with clinical outcome from a single institution. Analyzing plasma from 98 newly diagnosed patient with AML showed NPM1 mutation in 24 (23%) of patient while only one (4%) of 28 previously untreated patients with myelodysplastic syndrome (MDS) showed NPM1 mutation. Compared with peripheral blood cells, 2 (8%) of the 24 positive patients were negative by cells; none were positive by cells and negative by plasma. Most of the mutations detected (45%) were in patients with FAB classification M2, M4 and M5. In addition to the reported 4 bp insertion, we also detected 4 bp deletion in one patient in cells and plasma. Patients with NPM1 mutation had a significantly higher white blood cell count (P = 0.0009) and a higher blast count in peripheral blood (P = 0.002) and in bone marrow (P = 0.002). Blasts in patients with NPM1 mutant expressed lower levels of HLA-DR (P = 0.005), CD13 (P = 0.02) and CD34 (P < 0.0001), but higher CD33 levels (P = 0.0004). Patients with NPM1 mutation appear to have better chance of responding to standard therapy (P = 0.06). Event free survival of patients with NPM1 mutation was longer (P = 0.056) than in patients with intermediate cytogenetic abnormalities. The most striking difference in survival was in patients who required >35 days to respond to therapy (Figure). Survival was significantly longer in patients with NPM1 mutation requiring >35 days to respond (P = 0.027). This data not only support that NPM1 plays a significant role in the biology and clinical behavior of AML, but also show that plasma DNA is enriched with leukemia-specific DNA and is a reliable source for testing. Figure Figure

Gene Mutations, Their Interactions and Associations with Immunophenotypes of Leukemia Cells in Patients with Primary Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4138-4138
Author(s):  
Chien-Yuan Chen ◽  
Hsin-An Hou ◽  
Woei Tsay ◽  
Jih-Luh Tang ◽  
Liang-Inn Lin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Antigen Expression ◽  
Class Ii ◽  
Class I ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
I Gene ◽  
Acute Myeloid

Abstract The development of acute myeloid leukemia (AML) is a multistep process. Gilliland and colleagues proposed a two hit theory of leukemogenesis that requires collaboration of at least two classes of gene mutations. The Class I gene mutations activate the signal transduction pathway and confer proliferation and survival advantage to hematopoietic cells. The Class II gene mutations affect transcriptional activators or coactivators and serve to impair cell differentiation. In this study, comprehensive analyses of a panel of gene mutations, their interactions and associations with antigen expression of leukemia cells were performed in 324 patients with primary AML, including 275 adults and 49 children(≤18years). The gene mutations included FLT3/ ITD (78 cases, 24.1%), FLT/ TKD (24 cases, 7.4%), NPM(63 cases, 19.4%), CEBPA(45 cases, 13.9%), NRAS (39 cases, 12%), AML1 (31 cases, 9.6%), PTPN11 (14 cases, 4.3%), MLL/PTD(13 cases, 4%), KIT(10 cases, 3.1%), KRAS (8 cases, 2.5%), and JAK2 (3 cases, 0.9%). In addition, 33 patients had t(8;21), 24 had t(15;17), 9 had inv(16) and 13 had 11q23 translocations. Totally, the Class I gene mutations were detected in 155 patients (47.8%), and Class II gene mutations, in 228 patients (70.4%). Most Class II mutation was associated with a distinct immunophenotype of leukemic cells, such as CEBPA mutation: HLADR(+)CD7(+)CD15(+)CD19(−)CD34(+) (p<0.05), NPM mutation: HLADR(−)CD19(−)CD34(−)CD33(+)(p<0.05), AML1 mutation: HLADR(+)(p<0.05), MLL/PTD: CD7(−)(p<0.05), AML1/ETO: HLADR(+)CD7(−)CD19(+)CD33(−)CD34(+)CD56(+)(p<0.05), PML/RARA: HLADR(−)CD2(+)CD7(−)CD11b(−)CD34(−)(p<0.05), CBFB/MYH11: CD11b(+)CD14(+), and translocation 11q23: CD19(+)CD33(−)CD34(−) (p<0.05). The interactions between Class I and Class II mutations are shown in table 1. Among Class I mutations, FLT3/ ITD could interact with each subtype of Class II gene mutations, but were particularly associated with NPM mutations (p<0.001) and MLL/PTD (p=0.001). FLT3/ TKD was closely related to NPM mutations (p=0.03). Most KIT mutation were detected in the core binding factor leukemia (p<0.001). PTPN11 mutations were more frequently detected in patients with NPM mutations than in others (p=0.035). Few patients with complex cytogenetics revealed mutations of the gene panel studied (Table 1), suggesting that leukemogenesis in these patients was through mechanism other than the known Class I and Class II mutations. In this study, the cooperative gene alterations of the NUP98/HOXA9 fusion gene were demonstrated (Table1) which, to the best of our knowledge, have not been reported before. In conclusion, the development of AML requires multistep genetic changes. Most Class II mutation is closely associated with a distinct pattern of antigen expression of leukemic cells. Exploring the interactions of gene mutations may help us more understand the pathogenesis of leukemia and benefit further therapeutic strategy. Table I. Interaction of Class I and Class II gene mutations

Characterization of CEBPA Mutations in Acute Myeloid Leukemia in Taiwan - Most Patients with CEBPA Mutations Have Biallelic Mutations and Show a Distinct Immunophenotype of the Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4321-4321
Author(s):  
Liang In Lin ◽  
Chien Yuan Chen ◽  
Dong Tsamn Lin ◽  
You Chia Yeh ◽  
Hwei Fang Tien
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
Normal Karyotype ◽  
Leukemic Cells ◽  
Intermediate Risk ◽  
Hla Dr ◽  
Cebpa Mutations ◽  
Biallelic Mutations ◽  
Acute Myeloid

Abstract The transcription factor CCAAT/enhancer binding protein alpha (C/EBPa) encoded by the CEBPA gene, is crucial for the differentiation of immature granulocytes. Diminished or abnormal C/EBPa activity resulting from CEBPA gene mutations is widely known to contribute to the transformation of myeloid progenitors via reduction of their differentiation potential. The CEBPA mutations have been detected in approximately 7% of total acute myeloid leukemia (AML) and in 15% of those with intermediate-risk cytogenetics or those with normal karyotype. However, the age distribution of the patients with the CEBPA mutations and the immunophenotype of their leukemic cells are not known. Sequential studies of the CEBPA gene in AML patients are also limited. In this study, 104 patients with de novo acute myeloid leukemia (AML) were evaluated for the CEBPA mutation by direct sequencing. Excluding the silent mutations, 16 (15%) of the total 104 AML patients, 15 (25%) of the 61 patients with intermediate-risk cytogenetics and 11 (35%) of the 31 patients with normal karyotype showed CEBPA mutations, frequencies higher than those reported in the West. Further cloning and subsequent nucleotide sequence analysis revealed that 14 patients had heterozygous biallelic mutations: 11 had mutations involving both the N-terminal transactivation domain (TAD) and the C-terminal basic leucine zipper domain (bZIP) and three, in either the TAD region or the bZIP region. The remaining two patients had only one allele mutation in the TAD1 region. Most mutations in TAD region were repeat-number changes of simple sequence repeats and those in bZIP region were internal tandem duplications. Sequence analysis revealed that in the region spanning the bZIP mutations, there was hot spot for concensus topoisomerase II sites, which has also been shown in other AML-related mutations FLT3-ITD and MLL duplication. All but one patient with CEBPA mutations had M1 or M2 subtype of AML. The patients with CEBPA mutations had significantly higher incidences of CD7 (73%), CD15 (100%), CD34 (93%) and HLA-DR (93%) expression than others and the majority of them showed a distinct immunophenotype of the leukemic cells: HLA-DR+ CD7+ CD13+ CD14− CD15+ CD33+ CD34+. The incidence of the CEBPA mutation in children with AML was similar to that in adults. The CEBPA mutation was serially analyzed in 27 patients; the mutations disappeared at CR, but reappeared at relapse. No one developed novel mutation during the follow-up period. In conclusion, the CEBPA mutation may play an important role in the development, but not progression, of AML. The patients with the CEBPA mutations showed a distinct immunophenotype of the leukemic cells. Potential topoisomerase II cleavage sites locating in the bZIP region were first reported and we propose that this is relevant to the process of illegitimate recombination generating the internal tandem duplication pattern of bZIP mutations.

Prognostic Impact and Concurrent Genetic Alterations of CEBPA Double Mutations in Adults with Cytogenetically Intermediate-Risk Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2538-2538
Author(s):  
Shunichiro Yamaguchi ◽  
Kenji Tokunaga ◽  
Eisaku Iwanaga ◽  
Tomoko Nanri ◽  
Taizo Shimomura ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Disease Entity ◽  
Cebpa Mutations ◽  
Acute Myeloid

Abstract Abstract 2538 Aims: Among acute myeloid leukemia (AML) patients with intermediate-risk cytogenetics, C/EBPa mutations represent a distinct disease entity with a favorable clinical outcome and is adopted in the current WHO classification of AML as a provisional disease entity in the category AML with recurrent genetic abnormalities. CEBPA encodes a transcription factor that is essential for neutrophil development. AML patients with CEBPA mutations can be separated into two subgroups with a single mutation in the CEBPA (CEBPA sm) and double mutations (CEBPA dm). Biallelic mutations consisted of an N-terminal frameshift mutation and a C-terminal inframe bZIP mutation were detected in the majority of CEBPA dm, whereas CEBPA sm occurs in either N-terminal or C-terminal regions. More recent data indicate that favorable outcome is mainly observed in AML patients with CEBPA dm but not with CEBPA sm. In addition, concurrent gene mutations may occur more frequently in AML with CEBPA sm than in CEBPA dm. In contrast, transcription factor GATA2 mutations are frequently identified in AML with CEBPA dm. In this study, we examined incidence, concurrent gene mutations and clinical significance of CEBPA dm and CEBPA sm in Japanese adults with cytogenetically intermediate-risk AML. Methods: To identify the prevalence and prognostic impact of CEBPA dm and CEBPA sm, we examined 111 patients with intermediate-risk AML who were mainly treated with the JALSG protocols. Age ranged from 16 to 86 years, with a median of 58.5 years. DNA was extracted from bone marrow or peripheral blood mononuclear cells at diagnosis and subjected to PCR amplification and direct sequencing of the CEBPA, FLT3, NPM1, IDH1, IDH2, DNMT3A and GATA2 genes. This study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki. Results: Of 111 cytogenetically intermediate-risk AML, we found 12 (10.8%) CEBPA dm and 7 (6.3%) CEBPA sm. In 7 CEBPA sm, one NPM1 mutation and one FLT3-ITD were detected. Two FLT 3-ITD and no concurrent mutation of NPM1 were found in CEBPA dm. No mutation in the IDH1, IDH2, DNMT3A exon 23 was identified in both patients with CEBPA sm and CEBPA dm. On the other hand, mutations in the GATA2 zinc finger domains were detected in 3 of 12 (25%) patients with CEBPA dm. No GATA2 mutations were found in 7 CEBPA sm. One of 21 patients with wild-type CEBPA (CEBPA wt) had a GATA2 mutation. Patients with CEBPA double or single mutations showed a better 5-year overall survival (OS) compared to CEBPA wt (51.3% vs 16.0%, P=0.0048). CEBPA dm AML was associated with a significant superior clinical outcome compared with CEBPA wt (5-year OS, 55.6% vs 16.0%, P=0.0025). However, no significant difference was identified between CEBPA dm and CEBPA sm AML (5-years OS, 55.6% vs 42.9%, P=0.1375) or between CEBPA sm and CEBPA wt AML (5-year OS, 42.9% vs 16.0%, P=0.4827). In addition, the presence of additional GATA2 mutations did not significantly influence the clinical outcome of AML patients with CEBPA dm. Conclusions: A total of 19 (17.1%) patients with cytogenetically intermediate-risk AML harbored CEBPA mutations. Our study indicates that the presence of the CEBPA dm but not CEBPA sm is associated with favorable outcome in Japanese patients with cytogenetically intermediate-risk AML. Disclosures: No relevant conflicts of interest to declare.

CEBPA Germline Mutation Screening in Cytogenetically Normal Acute Myeloid Leukemia with Somatically Acquired CEBPA Mutations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 363-363
Author(s):  
Andrea Corbacioglu ◽  
Stefan Fröhling ◽  
Corinna Mendla ◽  
Karina Eiwen ◽  
Marianne Habdank ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Germline Mutation ◽  
Myeloid Leukemia ◽  
Mutation Screening ◽  
Family Members ◽  
Germline Mutations ◽  
Leukemic Cells ◽  
Insertion Mutation ◽  
Cebpa Mutations ◽  
Acute Myeloid

Abstract Background: Mutations in the myeloid transcription factor CEBPA (CCAAT enhancer binding protein-alpha) have been implicated in 10–15% of cytogenetically normal (CN) acute myeloid leukemia (AML) patients (pts). At the molecular level, two types of heterozygous CEPBA mutations have been identified. First, nonsense mutations affecting the N-terminal region, preventing the expression of the full-length protein, and second, in-frame mutations located in the basic-region-leucine zipper domain, resulting in a decreased CEBPA DNA-binding or dimerization activity. Clinically, CN-AML with mutant CEBPA is associated with a favorable prognosis. Recently, two independent families were reported in whom several family members affected by AML carried heterozygous germline CEBPA mutations. All germline mutations were located in the N-terminus. In addition, somatically acquired C-terminal mutations were detected in one out of three and two out of four family members, respectively. These findings led to the hypothesis that CEBPA germline mutations predispose to AML and that additional somatically acquired mutations may contribute to the development of the disease. Aim: To screen CN-AML pts with somatically acquired CEBPA mutations for germline CEBPA mutations as predisposing events for the development of AML. Methods: Pts were entered in the AML HD98-A or AMLSG 07-04 multicenter treatment trials of the German-Austrian AML Study Group. Buccal mucosa was obtained using commercial FTA filter cards after informed consent; CEBPA mutation screening was performed as recently described. Results: Buccal DNA from 18 pts exhibiting CEBPA mutations in their leukemic cells (biallelic N-terminal and C-terminal, n=12; heterozygous C-terminal, n=5; heterozygous N-terminal, n=1) was available for analysis. In 16 pts, no CEBPA germline mutations could be detected. In one pt, the heterozygous C-terminal in-frame mutation (1609G&gt;A) that was identified in the diagnostic sample was also present in the germline DNA. In a second pt with an N-terminal deletion and a C-terminal insertion mutation in the diagnostic sample, the N-terminal mutation was also identified in the germline material. Interestingly, the daughter of this pt also developed AML at the age of three years, exhibiting the identical N-terminal germline mutation, while the t C-terminal mutation was acquired and different to that of her mother. None of the remaining family members who could be analyzed had CEBPA germline mutations or a history of leukemia. Conclusion: The detection of CEBPA germline mutations in another pedigree with familial AML further sustains the hypothesis that CEBPA germline mutations might be the predisposing event in the development of AML in these families. Since other AML-associated gene mutations are rarely detected in CEBPA mutated cases, somatic mutations in the second allele represent a possible ‘second hit’ in this molecularly defined AML subtype.

scholarly journals Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5593-5603 ◽  
Author(s):  
Yang Shen ◽  
Yong-Mei Zhu ◽  
Xing Fan ◽  
Jing-Yi Shi ◽  
Qin-Rong Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Clinical Analysis ◽  
Prognostic Impact ◽  
Correlation Pattern ◽  
Cebpa Mutations ◽  
Gene Status ◽  
Relationship Of ◽  
Acute Myeloid

Abstract To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)–ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.

scholarly journals GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Philipp A. Greif ◽  
Annika Dufour ◽  
Nikola P. Konstandin ◽  
Bianka Ksienzyk ◽  
Evelyn Zellmeier ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Zinc Finger ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Distinct Subgroup ◽  
Cebpa Mutations ◽  
Acute Myeloid

Abstract Cytogenetically normal acute myeloid leukemia (CN-AML) with biallelic CEBPA gene mutations (biCEPBA) represents a distinct disease entity with a favorable clinical outcome. So far, it is not known whether other genetic alterations cooperate with biCEBPA mutations during leukemogenesis. To identify additional mutations, we performed whole exome sequencing of 5 biCEBPA patients and detected somatic GATA2 zinc finger 1 (ZF1) mutations in 2 of 5 cases. Both GATA2 and CEBPA are transcription factors crucial for hematopoietic development. Inherited or acquired mutations in both genes have been associated with leukemogenesis. Further mutational screening detected novel GATA2 ZF1 mutations in 13 of 33 biCEBPA-positive CN-AML patients (13/33, 39.4%). No GATA2 mutations were found in 38 CN-AML patients with a monoallelic CEBPA mutation and in 89 CN-AML patients with wild-type CEBPA status. The presence of additional GATA2 mutations (n=10) did not significantly influence the clinical outcome of 26 biCEBPA-positive patients. In reporter gene assays, all tested GATA2 ZF1 mutants showed reduced capacity to enhance CEBPA-mediated activation of transcription, suggesting that the GATA2 ZF1 mutations may collaborate with biCEPBA mutations to deregulate target genes during malignant transformation. We thus provide evidence for a genetically distinct subgroup of CN-AML. The German AML cooperative group trials 1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at www.clinicaltrials.gov.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid
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