41645a4e01a22e883eedf8333b961ecc 270522.pdf 8a1681f7830da72051ac63c99353f8d1f54a2381 270522.pdf 12c0f0da446f7edc19a6e6096ce74991ae70af837a8825b3f19eff263e45da75 270522.pdf Title: Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib Subject: The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate. Keywords: chronic myeloid leukemia; BCR-ABL1 transcripts; response to imatinib; survival; discontinuation; relapse-free survival Author: Sílvia Marcé, Blanca Xicoy, Olga García, Marta Cabezón, Natalia Estrada, Patricia Vélez, Concepción Boqué, Miguel Sagüés, Anna Angona, Raúl Teruel-Montoya, Francisca Ferrer-Marín, Paula Amat, Juan Carlos Hernández-Boluda, Mariana M. Ibarra, Eduardo Anguita, Montserrat Cortés, Andrés Fernández-Ruiz, Sandra Fontanals, Lurdes Zamora and on behalf of the Grupo Español de Leucemia Mieloide Crónica (GELMC) Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 20 13:12:03 2021 CEST ModDate: Tue Jul 20 13:24:21 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1192252 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HSNIKI+VnURWPalladioL Type 1 Custom yes yes no 10 0 SBTHBA+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 KGFTJX+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 RUBJTB+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 84 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 91 0 BLFMME+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 105 0 BLFMNG+PalatinoLinotype TrueType WinAnsi yes yes no 108 0 BLFMNI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 111 0 BLFMME+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 126 0 BLFMNG+PalatinoLinotype TrueType WinAnsi yes yes no 129 0 BLFMNI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 132 0 BLFMME+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 149 0 BLFMNG+PalatinoLinotype TrueType WinAnsi yes yes no 152 0 BLFMNI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 155 0 BLFMME+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 172 0 BLFMNG+PalatinoLinotype TrueType WinAnsi yes yes no 175 0 BLFMNI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 178 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:08:51 CEST RepresentationInformation: 270522.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:05:00 CEST Size: 1192252 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 363 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Material and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Patient Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Cytogenetic Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Determination of BCR-ABL1 Transcript Type Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Real-Time Quantitative PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Cytogenetics According to the Transcript Type Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Molecular Response by Transcript Type Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Effect of Transcript Type on Deep Molecular Response (DMR) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Prognostic Impact of Transcript Type on Overall Survival and CIP Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Analysis of TKI Discontinuation and Treatment-Free Remission (TFR) According to the Transcript Type Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Discussion and Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib Author: Sílvia Marcé, Blanca Xicoy, Olga García, Marta Cabezón, Natalia Estrada, Patricia Vélez, Concepción Boqué, Miguel Sagüés, Anna Angona, Raúl Teruel-Montoya, Francisca Ferrer-Marín, Paula Amat, Juan Carlos Hernández-Boluda, Mariana M. Ibarra, Eduardo Anguita, Montserrat Cortés, Andrés Fernández-Ruiz, Sandra Fontanals, Lurdes Zamora and on behalf of the Grupo Español de Leucemia Mieloide Crónica (GELMC) Subject: The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate. 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