Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia
FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outco...
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| Veröffentlicht in: | Cancer science 2018-12, Vol.109 (12), p.3981-3992 |
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| creator | Liu, Song‐Bai Qiu, Qiao‐Cheng Bao, Xie‐Bing Ma, Xiao Li, Hong‐Zhi Liu, Yue‐Jun Chen, Su‐Ning Song, Yao‐Hua Wu, De‐Pei Xue, Sheng‐Li |
| description | FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3‐ITD in‐frame duplication events remains unknown. Although there are some published studies investigating the FLT3‐ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3‐ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations. These findings may help to decipher the mechanisms of FLT3‐ITD in‐frame duplication events and stratify patients when considering different therapeutic combinations.
A total of 227 FLT3‐ITD sequences were analyzed from 227 Chinese adult de novo acute myeloid leukemia (AML) patients. ITD could be classified into 3 types based on molecular profiles. ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations. |
| doi_str_mv | 10.1111/cas.13835 |
| format | Article |
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A total of 227 FLT3‐ITD sequences were analyzed from 227 Chinese adult de novo acute myeloid leukemia (AML) patients. ITD could be classified into 3 types based on molecular profiles. ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13835</identifier><identifier>PMID: 30320942</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>acute myeloid leukemia ; Adult ; China ; Female ; FLT3‐ITD ; fms-Like Tyrosine Kinase 3 - chemistry ; fms-Like Tyrosine Kinase 3 - genetics ; Humans ; insertion sites ; kinase activity ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - therapy ; Male ; Middle Aged ; Mutagenesis, Insertional ; Original ; Prognosis ; prognostic value ; Protein Domains ; Remission Induction ; Sample Size ; Stem Cell Transplantation - methods ; Survival Analysis ; Tandem Repeat Sequences ; Transplantation, Homologous ; Young Adult</subject><ispartof>Cancer science, 2018-12, Vol.109 (12), p.3981-3992</ispartof><rights>2018 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-3920-1032</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272103/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272103/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30320942$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Song‐Bai</creatorcontrib><creatorcontrib>Qiu, Qiao‐Cheng</creatorcontrib><creatorcontrib>Bao, Xie‐Bing</creatorcontrib><creatorcontrib>Ma, Xiao</creatorcontrib><creatorcontrib>Li, Hong‐Zhi</creatorcontrib><creatorcontrib>Liu, Yue‐Jun</creatorcontrib><creatorcontrib>Chen, Su‐Ning</creatorcontrib><creatorcontrib>Song, Yao‐Hua</creatorcontrib><creatorcontrib>Wu, De‐Pei</creatorcontrib><creatorcontrib>Xue, Sheng‐Li</creatorcontrib><title>Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3‐ITD in‐frame duplication events remains unknown. Although there are some published studies investigating the FLT3‐ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3‐ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations. These findings may help to decipher the mechanisms of FLT3‐ITD in‐frame duplication events and stratify patients when considering different therapeutic combinations.
A total of 227 FLT3‐ITD sequences were analyzed from 227 Chinese adult de novo acute myeloid leukemia (AML) patients. ITD could be classified into 3 types based on molecular profiles. ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations.</description><subject>acute myeloid leukemia</subject><subject>Adult</subject><subject>China</subject><subject>Female</subject><subject>FLT3‐ITD</subject><subject>fms-Like Tyrosine Kinase 3 - chemistry</subject><subject>fms-Like Tyrosine Kinase 3 - genetics</subject><subject>Humans</subject><subject>insertion sites</subject><subject>kinase activity</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutagenesis, Insertional</subject><subject>Original</subject><subject>Prognosis</subject><subject>prognostic value</subject><subject>Protein Domains</subject><subject>Remission Induction</subject><subject>Sample Size</subject><subject>Stem Cell Transplantation - methods</subject><subject>Survival Analysis</subject><subject>Tandem Repeat Sequences</subject><subject>Transplantation, Homologous</subject><subject>Young Adult</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIlsKBH0D-gbR2nOcFqSoUKlUCiXK2NvGmdUnsKnGKeuMT-Ea-hNACgr3saGd2DjOEXHI25N2McmiGXCQiPCJ9LoLUixmLjvc49lIm_B45a5o1YyIK0uCU9ER3Y2ng94l6BOewNhSMopvaLo1tnM7pFsoWqS3odL4QH2_vs8UNrVoHTlvTUG3oZKUNNkgVUmO3loJqS0chbx3Saoel1YqW2L5gpeGcnBRQNnjxvQfkeXq7mNx784e72WQ899YiCkMvSjFNORY8yJIkzmMUfhbHIQieCMYxhgQKFWaQFUkESS5yFopAMYUAuQIGYkCuD76bNqtQ5WhcDaXc1LqCeictaPmfMXoll3YrIz_2OROdwdVfg9_Pn7w6weggeNUl7n55zuRXEbIrQu6LkJPx0x6IT8Ddfgo</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Liu, Song‐Bai</creator><creator>Qiu, Qiao‐Cheng</creator><creator>Bao, Xie‐Bing</creator><creator>Ma, Xiao</creator><creator>Li, Hong‐Zhi</creator><creator>Liu, Yue‐Jun</creator><creator>Chen, Su‐Ning</creator><creator>Song, Yao‐Hua</creator><creator>Wu, De‐Pei</creator><creator>Xue, Sheng‐Li</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3920-1032</orcidid></search><sort><creationdate>201812</creationdate><title>Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia</title><author>Liu, Song‐Bai ; Qiu, Qiao‐Cheng ; Bao, Xie‐Bing ; Ma, Xiao ; Li, Hong‐Zhi ; Liu, Yue‐Jun ; Chen, Su‐Ning ; Song, Yao‐Hua ; Wu, De‐Pei ; Xue, Sheng‐Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j3655-69e991ef14b887c7e32b775a318301e7a8afd5babf86a8c3c0534d0deaacda0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>acute myeloid leukemia</topic><topic>Adult</topic><topic>China</topic><topic>Female</topic><topic>FLT3‐ITD</topic><topic>fms-Like Tyrosine Kinase 3 - chemistry</topic><topic>fms-Like Tyrosine Kinase 3 - genetics</topic><topic>Humans</topic><topic>insertion sites</topic><topic>kinase activity</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutagenesis, Insertional</topic><topic>Original</topic><topic>Prognosis</topic><topic>prognostic value</topic><topic>Protein Domains</topic><topic>Remission Induction</topic><topic>Sample Size</topic><topic>Stem Cell Transplantation - methods</topic><topic>Survival Analysis</topic><topic>Tandem Repeat Sequences</topic><topic>Transplantation, Homologous</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Song‐Bai</creatorcontrib><creatorcontrib>Qiu, Qiao‐Cheng</creatorcontrib><creatorcontrib>Bao, Xie‐Bing</creatorcontrib><creatorcontrib>Ma, Xiao</creatorcontrib><creatorcontrib>Li, Hong‐Zhi</creatorcontrib><creatorcontrib>Liu, Yue‐Jun</creatorcontrib><creatorcontrib>Chen, Su‐Ning</creatorcontrib><creatorcontrib>Song, Yao‐Hua</creatorcontrib><creatorcontrib>Wu, De‐Pei</creatorcontrib><creatorcontrib>Xue, Sheng‐Li</creatorcontrib><collection>Wiley Online Library</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Song‐Bai</au><au>Qiu, Qiao‐Cheng</au><au>Bao, Xie‐Bing</au><au>Ma, Xiao</au><au>Li, Hong‐Zhi</au><au>Liu, Yue‐Jun</au><au>Chen, Su‐Ning</au><au>Song, Yao‐Hua</au><au>Wu, De‐Pei</au><au>Xue, Sheng‐Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2018-12</date><risdate>2018</risdate><volume>109</volume><issue>12</issue><spage>3981</spage><epage>3992</epage><pages>3981-3992</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>FMS‐like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3‐ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two‐thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3‐ITD in‐frame duplication events remains unknown. Although there are some published studies investigating the FLT3‐ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3‐ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations. These findings may help to decipher the mechanisms of FLT3‐ITD in‐frame duplication events and stratify patients when considering different therapeutic combinations.
A total of 227 FLT3‐ITD sequences were analyzed from 227 Chinese adult de novo acute myeloid leukemia (AML) patients. ITD could be classified into 3 types based on molecular profiles. ITD integration sites in the hinge region or beta1‐sheet region are an unfavorable prognostic factor in adult AML patients with FLT3‐ITD mutations.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>30320942</pmid><doi>10.1111/cas.13835</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3920-1032</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | acute myeloid leukemia Adult China Female FLT3‐ITD fms-Like Tyrosine Kinase 3 - chemistry fms-Like Tyrosine Kinase 3 - genetics Humans insertion sites kinase activity Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - therapy Male Middle Aged Mutagenesis, Insertional Original Prognosis prognostic value Protein Domains Remission Induction Sample Size Stem Cell Transplantation - methods Survival Analysis Tandem Repeat Sequences Transplantation, Homologous Young Adult |
| title | Pattern and prognostic value of FLT3‐ITD mutations in Chinese de novo adult acute myeloid leukemia |
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