Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation
Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mut AML. Therefore, more expeditious diagnostic approaches may contribute to...
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| creator | Matarraz, Sergio Leoz, Pilar Calvo, Xavier García Alonso, Luis Ayala Bueno, Rosa Sánchez-Gallego, José Ignacio Villamor, Neus Colado, Enrique Belén Vidriales, María Prieto Conde, María Isabel Chillon, Maria Carmen García-Sanz, Ramón Van Der Velden, Vincent H.J. López Cadenas, Félix Díez-Campelo, María Arenillas, Leonor Alonso, Sara Fonseca, Ariana Quirós Caso, Covadonga Magnano, Laura Garcia Vela, José Antonio Fernandez, Carlos Damasceno, Daniela Mayado, Andrea Barrena, Susana Orfao, Alberto |
| description | Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mut AML. Therefore, more expeditious diagnostic approaches may contribute to early diagnosis and prognostic stratification of these patients. Herein, we investigated the association of immunophenotypic features of leukemic and monocytic cells with the presence of NPM1mut in AML.
Methods. A total of 404 bone marrow (BM) samples from newly-diagnosed AML patients according to WHO 2017 classification were retrospectively studied by 8-color flow cytometry, including 225 AML with NPM1mut and 179 cases wild type gene (NPM1wt). Information on FLT3-ITD could be obtained from 397/404 cases. Thus, FLT3-ITDmut was present in 85/397 (21%), being concomitant with NPM1mut in 62/85 AML cases (73%). Logistic regression analysis was used to identify predictive phenotypes for the presence of NPM1mut.
Results. Overall, blast cell with immunophenotypic features of monocytic differentiation (corresponding to FAB M4 and M5 AML subtypes) were observed among 135/225 (60%) and 69/179 (38.5%) AML patients with NPM1mut and NPM1wt, respectively (p |
| doi_str_mv | 10.1182/blood-2019-131733 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2019_131733</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497118606160</els_id><sourcerecordid>S0006497118606160</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1373-67908b5634c4eae6d4c3de9f73fa40cda1f8f49d6448b1c4f28e33197bcc8cc53</originalsourceid><addsrcrecordid>eNp9kE1OwzAQRi0EEqVwAHa-QMCO3fyIVVVBW6kFFrC2kvGYGhK7shOkXIBzk1LYshpppPd9M4-Qa85uOC_S27rxXicp42XCBc-FOCETPkuLhLGUnZIJYyxLZJnzc3IR4ztjXIp0NiFf86bDgJqu27Z3fr9D57thj5F6RzfYf2BrgVZO3_pAt955GLpxscCmidQE39I59B3S7YCNt_oPqejKvu2agT6P2RY6akb8sYcGxwofW-voEt2I9V3VWe8uyZmpmohXv3NKXh_uXxarZPO0XC_mmwS4yEWS5SUr6lkmJEisMNMShMbS5MJUkoGuuCmMLHUmZVFzkCYtUAhe5jVAATATU8KPuRB8jAGN2gfbVmFQnKmDSPUjUh1EqqPIkbk7Mjge9mkxqAgWHYyPBYROaW__ob8BU3Z-lQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Matarraz, Sergio ; Leoz, Pilar ; Calvo, Xavier ; García Alonso, Luis ; Ayala Bueno, Rosa ; Sánchez-Gallego, José Ignacio ; Villamor, Neus ; Colado, Enrique ; Belén Vidriales, María ; Prieto Conde, María Isabel ; Chillon, Maria Carmen ; García-Sanz, Ramón ; Van Der Velden, Vincent H.J. ; López Cadenas, Félix ; Díez-Campelo, María ; Arenillas, Leonor ; Alonso, Sara ; Fonseca, Ariana ; Quirós Caso, Covadonga ; Magnano, Laura ; Garcia Vela, José Antonio ; Fernandez, Carlos ; Damasceno, Daniela ; Mayado, Andrea ; Barrena, Susana ; Orfao, Alberto</creator><creatorcontrib>Matarraz, Sergio ; Leoz, Pilar ; Calvo, Xavier ; García Alonso, Luis ; Ayala Bueno, Rosa ; Sánchez-Gallego, José Ignacio ; Villamor, Neus ; Colado, Enrique ; Belén Vidriales, María ; Prieto Conde, María Isabel ; Chillon, Maria Carmen ; García-Sanz, Ramón ; Van Der Velden, Vincent H.J. ; López Cadenas, Félix ; Díez-Campelo, María ; Arenillas, Leonor ; Alonso, Sara ; Fonseca, Ariana ; Quirós Caso, Covadonga ; Magnano, Laura ; Garcia Vela, José Antonio ; Fernandez, Carlos ; Damasceno, Daniela ; Mayado, Andrea ; Barrena, Susana ; Orfao, Alberto</creatorcontrib><description><![CDATA[Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mut AML. Therefore, more expeditious diagnostic approaches may contribute to early diagnosis and prognostic stratification of these patients. Herein, we investigated the association of immunophenotypic features of leukemic and monocytic cells with the presence of NPM1mut in AML.
Methods. A total of 404 bone marrow (BM) samples from newly-diagnosed AML patients according to WHO 2017 classification were retrospectively studied by 8-color flow cytometry, including 225 AML with NPM1mut and 179 cases wild type gene (NPM1wt). Information on FLT3-ITD could be obtained from 397/404 cases. Thus, FLT3-ITDmut was present in 85/397 (21%), being concomitant with NPM1mut in 62/85 AML cases (73%). Logistic regression analysis was used to identify predictive phenotypes for the presence of NPM1mut.
Results. Overall, blast cell with immunophenotypic features of monocytic differentiation (corresponding to FAB M4 and M5 AML subtypes) were observed among 135/225 (60%) and 69/179 (38.5%) AML patients with NPM1mut and NPM1wt, respectively (p<0.001). In the remaining AML cases without monocytic differentiation (FAB M0, M1 and M2; n=200), both immature/myeloid blasts and remaining monocytic cells were immunophenotypically characterized.
Among AML with monocytic blast cell differentiation, altered monocytic phenotypes were more frequent among NPM1mut vs. NPM1wt cases (98% vs. 36%) (p<0.001). In detail, these phenotypic alterations consisted of asynchronous expression of CD300e prior CD14 (79% vs. 5% NPM1wt cases, respectively; p<0.001) and/or CD35 prior CD14 (84% vs. 30%), which were observed independently of FLT3-ITD. Of note, coexistence of the latter two asynchronous monocytic patterns (CD300e prior CD14 and CD35 prior CD14) on monocytic blast cells was specific for NPM1mut (64% vs. 0% NPM1wt patients; p<0.001).
Noteworthy, in AML cases without blast cell monocytic differentiation, remaining monocytic cells showed similar asynchronous phenotypic patterns, which were also more frequent among NPM1mut cases (78% vs. 23% of NPM1wt cases, respectively; p <0.001). Thus, remaining monocytic cells from NPM1mut AML cases also showed a higher frequency of asynchronous CD300e prior CD14 (64% vs. 8% of NPM1wt cases; p<0.001) and CD35 prior CD14 expression (58% vs. 20% of NPM1wt cases, respectively; p<0.001).
In addition, aberrant CD9 blast cell expression was found in a significant proportion of all AML cases studied (124/222, 56%). However, altered CD9 was more frequent on (either monocytic or immature/myeloid) blast cells from AML cases with NPM1mut (76% vs. 46% NPM1wt cases; p<0.001), but not in AML with only-FLT3-ITDmut (39% vs. 46% of NPM1wtFLT3-ITDwt; p>0.05). In turn, aberrant CD25 expression on blast cells was otherwise linked to FLT3-ITDmut (61% vs. 20% of FLT3-ITDwt cases; p<0.001), being more frequent in AML with FLT3-ITDmutNPM1wt and double mutated AML cases vs. AML with FLT3-ITDwtNPM1mut and FLT3-ITDwtNPM1wt (79% and 47% vs. 20% and 20% of cases, respectively; p<0.001). In addition, overall, FLT3-ITDmut was associated with a significantly higher proportion of immature (i.e. CD34+) blasts, as compared to FLT3-ITDwt cases (median of 10% vs. 0.3% CD34+ blasts; p<0.001).
In multivariate analysis, baseline detection of monocytic-lineage blast cells with asynchronous expression of CD300 prior CD14 -C-index= 0.954, odds ratio (OR), 78.8; 95% confidence interval (CI), 13.1-471; p<0.001- and CD35 prior CD14 (OR, 24.5; 95% CI, 4.8-123; p<0.001) and detection of these asynchronous patterns on remaining monocytic cells from AML without monocytic differentiation (C-index= 0.816, OR, 14.7; 95% CI, 6.4-34; p<0.001 and, OR, 2.5; 95% CI, 1.2-5.3; p=0.01, respectively) showed the highest predictive value for NPM1mut in AML. In turn, CD25 aberrant blast cell expression was the only immunophenotypic parameter with predictive value for FLT3-ITDmut (OR, 6.4; 95% CI, 2.9-14.5; p<0.001).
Conclusions. Detection of specific aberrant immunophenotypic patterns among blast cells and/or remaining monocytic cells from AML patients is highly predictive for NPM1mut, which may contribute to early diagnosis and follow-up of these patients.
Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.]]></description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2019-131733</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2019-11, Vol.134 (Supplement_1), p.2687-2687</ispartof><rights>2019 American Society of Hematology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids></links><search><creatorcontrib>Matarraz, Sergio</creatorcontrib><creatorcontrib>Leoz, Pilar</creatorcontrib><creatorcontrib>Calvo, Xavier</creatorcontrib><creatorcontrib>García Alonso, Luis</creatorcontrib><creatorcontrib>Ayala Bueno, Rosa</creatorcontrib><creatorcontrib>Sánchez-Gallego, José Ignacio</creatorcontrib><creatorcontrib>Villamor, Neus</creatorcontrib><creatorcontrib>Colado, Enrique</creatorcontrib><creatorcontrib>Belén Vidriales, María</creatorcontrib><creatorcontrib>Prieto Conde, María Isabel</creatorcontrib><creatorcontrib>Chillon, Maria Carmen</creatorcontrib><creatorcontrib>García-Sanz, Ramón</creatorcontrib><creatorcontrib>Van Der Velden, Vincent H.J.</creatorcontrib><creatorcontrib>López Cadenas, Félix</creatorcontrib><creatorcontrib>Díez-Campelo, María</creatorcontrib><creatorcontrib>Arenillas, Leonor</creatorcontrib><creatorcontrib>Alonso, Sara</creatorcontrib><creatorcontrib>Fonseca, Ariana</creatorcontrib><creatorcontrib>Quirós Caso, Covadonga</creatorcontrib><creatorcontrib>Magnano, Laura</creatorcontrib><creatorcontrib>Garcia Vela, José Antonio</creatorcontrib><creatorcontrib>Fernandez, Carlos</creatorcontrib><creatorcontrib>Damasceno, Daniela</creatorcontrib><creatorcontrib>Mayado, Andrea</creatorcontrib><creatorcontrib>Barrena, Susana</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><title>Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation</title><title>Blood</title><description><![CDATA[Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mut AML. Therefore, more expeditious diagnostic approaches may contribute to early diagnosis and prognostic stratification of these patients. Herein, we investigated the association of immunophenotypic features of leukemic and monocytic cells with the presence of NPM1mut in AML.
Methods. A total of 404 bone marrow (BM) samples from newly-diagnosed AML patients according to WHO 2017 classification were retrospectively studied by 8-color flow cytometry, including 225 AML with NPM1mut and 179 cases wild type gene (NPM1wt). Information on FLT3-ITD could be obtained from 397/404 cases. Thus, FLT3-ITDmut was present in 85/397 (21%), being concomitant with NPM1mut in 62/85 AML cases (73%). Logistic regression analysis was used to identify predictive phenotypes for the presence of NPM1mut.
Results. Overall, blast cell with immunophenotypic features of monocytic differentiation (corresponding to FAB M4 and M5 AML subtypes) were observed among 135/225 (60%) and 69/179 (38.5%) AML patients with NPM1mut and NPM1wt, respectively (p<0.001). In the remaining AML cases without monocytic differentiation (FAB M0, M1 and M2; n=200), both immature/myeloid blasts and remaining monocytic cells were immunophenotypically characterized.
Among AML with monocytic blast cell differentiation, altered monocytic phenotypes were more frequent among NPM1mut vs. NPM1wt cases (98% vs. 36%) (p<0.001). In detail, these phenotypic alterations consisted of asynchronous expression of CD300e prior CD14 (79% vs. 5% NPM1wt cases, respectively; p<0.001) and/or CD35 prior CD14 (84% vs. 30%), which were observed independently of FLT3-ITD. Of note, coexistence of the latter two asynchronous monocytic patterns (CD300e prior CD14 and CD35 prior CD14) on monocytic blast cells was specific for NPM1mut (64% vs. 0% NPM1wt patients; p<0.001).
Noteworthy, in AML cases without blast cell monocytic differentiation, remaining monocytic cells showed similar asynchronous phenotypic patterns, which were also more frequent among NPM1mut cases (78% vs. 23% of NPM1wt cases, respectively; p <0.001). Thus, remaining monocytic cells from NPM1mut AML cases also showed a higher frequency of asynchronous CD300e prior CD14 (64% vs. 8% of NPM1wt cases; p<0.001) and CD35 prior CD14 expression (58% vs. 20% of NPM1wt cases, respectively; p<0.001).
In addition, aberrant CD9 blast cell expression was found in a significant proportion of all AML cases studied (124/222, 56%). However, altered CD9 was more frequent on (either monocytic or immature/myeloid) blast cells from AML cases with NPM1mut (76% vs. 46% NPM1wt cases; p<0.001), but not in AML with only-FLT3-ITDmut (39% vs. 46% of NPM1wtFLT3-ITDwt; p>0.05). In turn, aberrant CD25 expression on blast cells was otherwise linked to FLT3-ITDmut (61% vs. 20% of FLT3-ITDwt cases; p<0.001), being more frequent in AML with FLT3-ITDmutNPM1wt and double mutated AML cases vs. AML with FLT3-ITDwtNPM1mut and FLT3-ITDwtNPM1wt (79% and 47% vs. 20% and 20% of cases, respectively; p<0.001). In addition, overall, FLT3-ITDmut was associated with a significantly higher proportion of immature (i.e. CD34+) blasts, as compared to FLT3-ITDwt cases (median of 10% vs. 0.3% CD34+ blasts; p<0.001).
In multivariate analysis, baseline detection of monocytic-lineage blast cells with asynchronous expression of CD300 prior CD14 -C-index= 0.954, odds ratio (OR), 78.8; 95% confidence interval (CI), 13.1-471; p<0.001- and CD35 prior CD14 (OR, 24.5; 95% CI, 4.8-123; p<0.001) and detection of these asynchronous patterns on remaining monocytic cells from AML without monocytic differentiation (C-index= 0.816, OR, 14.7; 95% CI, 6.4-34; p<0.001 and, OR, 2.5; 95% CI, 1.2-5.3; p=0.01, respectively) showed the highest predictive value for NPM1mut in AML. In turn, CD25 aberrant blast cell expression was the only immunophenotypic parameter with predictive value for FLT3-ITDmut (OR, 6.4; 95% CI, 2.9-14.5; p<0.001).
Conclusions. Detection of specific aberrant immunophenotypic patterns among blast cells and/or remaining monocytic cells from AML patients is highly predictive for NPM1mut, which may contribute to early diagnosis and follow-up of these patients.
Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.]]></description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kE1OwzAQRi0EEqVwAHa-QMCO3fyIVVVBW6kFFrC2kvGYGhK7shOkXIBzk1LYshpppPd9M4-Qa85uOC_S27rxXicp42XCBc-FOCETPkuLhLGUnZIJYyxLZJnzc3IR4ztjXIp0NiFf86bDgJqu27Z3fr9D57thj5F6RzfYf2BrgVZO3_pAt955GLpxscCmidQE39I59B3S7YCNt_oPqejKvu2agT6P2RY6akb8sYcGxwofW-voEt2I9V3VWe8uyZmpmohXv3NKXh_uXxarZPO0XC_mmwS4yEWS5SUr6lkmJEisMNMShMbS5MJUkoGuuCmMLHUmZVFzkCYtUAhe5jVAATATU8KPuRB8jAGN2gfbVmFQnKmDSPUjUh1EqqPIkbk7Mjge9mkxqAgWHYyPBYROaW__ob8BU3Z-lQ</recordid><startdate>20191113</startdate><enddate>20191113</enddate><creator>Matarraz, Sergio</creator><creator>Leoz, Pilar</creator><creator>Calvo, Xavier</creator><creator>García Alonso, Luis</creator><creator>Ayala Bueno, Rosa</creator><creator>Sánchez-Gallego, José Ignacio</creator><creator>Villamor, Neus</creator><creator>Colado, Enrique</creator><creator>Belén Vidriales, María</creator><creator>Prieto Conde, María Isabel</creator><creator>Chillon, Maria Carmen</creator><creator>García-Sanz, Ramón</creator><creator>Van Der Velden, Vincent H.J.</creator><creator>López Cadenas, Félix</creator><creator>Díez-Campelo, María</creator><creator>Arenillas, Leonor</creator><creator>Alonso, Sara</creator><creator>Fonseca, Ariana</creator><creator>Quirós Caso, Covadonga</creator><creator>Magnano, Laura</creator><creator>Garcia Vela, José Antonio</creator><creator>Fernandez, Carlos</creator><creator>Damasceno, Daniela</creator><creator>Mayado, Andrea</creator><creator>Barrena, Susana</creator><creator>Orfao, Alberto</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20191113</creationdate><title>Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation</title><author>Matarraz, Sergio ; Leoz, Pilar ; Calvo, Xavier ; García Alonso, Luis ; Ayala Bueno, Rosa ; Sánchez-Gallego, José Ignacio ; Villamor, Neus ; Colado, Enrique ; Belén Vidriales, María ; Prieto Conde, María Isabel ; Chillon, Maria Carmen ; García-Sanz, Ramón ; Van Der Velden, Vincent H.J. ; López Cadenas, Félix ; Díez-Campelo, María ; Arenillas, Leonor ; Alonso, Sara ; Fonseca, Ariana ; Quirós Caso, Covadonga ; Magnano, Laura ; Garcia Vela, José Antonio ; Fernandez, Carlos ; Damasceno, Daniela ; Mayado, Andrea ; Barrena, Susana ; Orfao, Alberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1373-67908b5634c4eae6d4c3de9f73fa40cda1f8f49d6448b1c4f28e33197bcc8cc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matarraz, Sergio</creatorcontrib><creatorcontrib>Leoz, Pilar</creatorcontrib><creatorcontrib>Calvo, Xavier</creatorcontrib><creatorcontrib>García Alonso, Luis</creatorcontrib><creatorcontrib>Ayala Bueno, Rosa</creatorcontrib><creatorcontrib>Sánchez-Gallego, José Ignacio</creatorcontrib><creatorcontrib>Villamor, Neus</creatorcontrib><creatorcontrib>Colado, Enrique</creatorcontrib><creatorcontrib>Belén Vidriales, María</creatorcontrib><creatorcontrib>Prieto Conde, María Isabel</creatorcontrib><creatorcontrib>Chillon, Maria Carmen</creatorcontrib><creatorcontrib>García-Sanz, Ramón</creatorcontrib><creatorcontrib>Van Der Velden, Vincent H.J.</creatorcontrib><creatorcontrib>López Cadenas, Félix</creatorcontrib><creatorcontrib>Díez-Campelo, María</creatorcontrib><creatorcontrib>Arenillas, Leonor</creatorcontrib><creatorcontrib>Alonso, Sara</creatorcontrib><creatorcontrib>Fonseca, Ariana</creatorcontrib><creatorcontrib>Quirós Caso, Covadonga</creatorcontrib><creatorcontrib>Magnano, Laura</creatorcontrib><creatorcontrib>Garcia Vela, José Antonio</creatorcontrib><creatorcontrib>Fernandez, Carlos</creatorcontrib><creatorcontrib>Damasceno, Daniela</creatorcontrib><creatorcontrib>Mayado, Andrea</creatorcontrib><creatorcontrib>Barrena, Susana</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matarraz, Sergio</au><au>Leoz, Pilar</au><au>Calvo, Xavier</au><au>García Alonso, Luis</au><au>Ayala Bueno, Rosa</au><au>Sánchez-Gallego, José Ignacio</au><au>Villamor, Neus</au><au>Colado, Enrique</au><au>Belén Vidriales, María</au><au>Prieto Conde, María Isabel</au><au>Chillon, Maria Carmen</au><au>García-Sanz, Ramón</au><au>Van Der Velden, Vincent H.J.</au><au>López Cadenas, Félix</au><au>Díez-Campelo, María</au><au>Arenillas, Leonor</au><au>Alonso, Sara</au><au>Fonseca, Ariana</au><au>Quirós Caso, Covadonga</au><au>Magnano, Laura</au><au>Garcia Vela, José Antonio</au><au>Fernandez, Carlos</au><au>Damasceno, Daniela</au><au>Mayado, Andrea</au><au>Barrena, Susana</au><au>Orfao, Alberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation</atitle><jtitle>Blood</jtitle><date>2019-11-13</date><risdate>2019</risdate><volume>134</volume><issue>Supplement_1</issue><spage>2687</spage><epage>2687</epage><pages>2687-2687</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract><![CDATA[Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mut AML. Therefore, more expeditious diagnostic approaches may contribute to early diagnosis and prognostic stratification of these patients. Herein, we investigated the association of immunophenotypic features of leukemic and monocytic cells with the presence of NPM1mut in AML.
Methods. A total of 404 bone marrow (BM) samples from newly-diagnosed AML patients according to WHO 2017 classification were retrospectively studied by 8-color flow cytometry, including 225 AML with NPM1mut and 179 cases wild type gene (NPM1wt). Information on FLT3-ITD could be obtained from 397/404 cases. Thus, FLT3-ITDmut was present in 85/397 (21%), being concomitant with NPM1mut in 62/85 AML cases (73%). Logistic regression analysis was used to identify predictive phenotypes for the presence of NPM1mut.
Results. Overall, blast cell with immunophenotypic features of monocytic differentiation (corresponding to FAB M4 and M5 AML subtypes) were observed among 135/225 (60%) and 69/179 (38.5%) AML patients with NPM1mut and NPM1wt, respectively (p<0.001). In the remaining AML cases without monocytic differentiation (FAB M0, M1 and M2; n=200), both immature/myeloid blasts and remaining monocytic cells were immunophenotypically characterized.
Among AML with monocytic blast cell differentiation, altered monocytic phenotypes were more frequent among NPM1mut vs. NPM1wt cases (98% vs. 36%) (p<0.001). In detail, these phenotypic alterations consisted of asynchronous expression of CD300e prior CD14 (79% vs. 5% NPM1wt cases, respectively; p<0.001) and/or CD35 prior CD14 (84% vs. 30%), which were observed independently of FLT3-ITD. Of note, coexistence of the latter two asynchronous monocytic patterns (CD300e prior CD14 and CD35 prior CD14) on monocytic blast cells was specific for NPM1mut (64% vs. 0% NPM1wt patients; p<0.001).
Noteworthy, in AML cases without blast cell monocytic differentiation, remaining monocytic cells showed similar asynchronous phenotypic patterns, which were also more frequent among NPM1mut cases (78% vs. 23% of NPM1wt cases, respectively; p <0.001). Thus, remaining monocytic cells from NPM1mut AML cases also showed a higher frequency of asynchronous CD300e prior CD14 (64% vs. 8% of NPM1wt cases; p<0.001) and CD35 prior CD14 expression (58% vs. 20% of NPM1wt cases, respectively; p<0.001).
In addition, aberrant CD9 blast cell expression was found in a significant proportion of all AML cases studied (124/222, 56%). However, altered CD9 was more frequent on (either monocytic or immature/myeloid) blast cells from AML cases with NPM1mut (76% vs. 46% NPM1wt cases; p<0.001), but not in AML with only-FLT3-ITDmut (39% vs. 46% of NPM1wtFLT3-ITDwt; p>0.05). In turn, aberrant CD25 expression on blast cells was otherwise linked to FLT3-ITDmut (61% vs. 20% of FLT3-ITDwt cases; p<0.001), being more frequent in AML with FLT3-ITDmutNPM1wt and double mutated AML cases vs. AML with FLT3-ITDwtNPM1mut and FLT3-ITDwtNPM1wt (79% and 47% vs. 20% and 20% of cases, respectively; p<0.001). In addition, overall, FLT3-ITDmut was associated with a significantly higher proportion of immature (i.e. CD34+) blasts, as compared to FLT3-ITDwt cases (median of 10% vs. 0.3% CD34+ blasts; p<0.001).
In multivariate analysis, baseline detection of monocytic-lineage blast cells with asynchronous expression of CD300 prior CD14 -C-index= 0.954, odds ratio (OR), 78.8; 95% confidence interval (CI), 13.1-471; p<0.001- and CD35 prior CD14 (OR, 24.5; 95% CI, 4.8-123; p<0.001) and detection of these asynchronous patterns on remaining monocytic cells from AML without monocytic differentiation (C-index= 0.816, OR, 14.7; 95% CI, 6.4-34; p<0.001 and, OR, 2.5; 95% CI, 1.2-5.3; p=0.01, respectively) showed the highest predictive value for NPM1mut in AML. In turn, CD25 aberrant blast cell expression was the only immunophenotypic parameter with predictive value for FLT3-ITDmut (OR, 6.4; 95% CI, 2.9-14.5; p<0.001).
Conclusions. Detection of specific aberrant immunophenotypic patterns among blast cells and/or remaining monocytic cells from AML patients is highly predictive for NPM1mut, which may contribute to early diagnosis and follow-up of these patients.
Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.]]></abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2019-131733</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2019-11, Vol.134 (Supplement_1), p.2687-2687 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_crossref_primary_10_1182_blood_2019_131733 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| title | Altered Immunophenotypes on Leukemic and/or Monocytic Cells from Acute Myeloid Leukemia Highly Predict for Nucleophosmin Gene Mutation |
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