Leukemic Cellular Retinoic Acid Resistance and Missense Mutations in the PML-RAR Fusion Gene After Relapse of Acute Promyelocytic Leukemia From Treatment.

Slides:

Advertisements

Similar presentations

Figure 1. RT–PCR identification of an abnormal transcript of the PTPN6 gene in normal and leukemic bone marrow cells and cell line. (a) Diagrammatic representation.

Advertisements

Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A by Richard D. Bagnall, Naushin Waseem, Peter M.

Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21 by Liat Rainis, Dan Bercovich, Sabine Strehl, Andrea.

Pre-Clinical Validation of a Novel, Highly Sensitive Assay to Detect PML-RARα mRNA Using Real-Time Reverse-Transcription Polymerase Chain Reaction James.

Characterization of the Human Platelet/Endothelial Cell Adhesion Molecule-1 Promoter: Identification of a GATA-2 Binding Element Required for Optimal Transcriptional.

by Nancy D. Borson, Martha Q. Lacy, and Peter J. Wettstein

Alternative Splicing of a Novel Glycophorin Allele GPHe(GL) Generates Two Protein Isoforms in the Human Erythrocyte Membrane by Cheng-Han Huang, Olga O.

Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center.

Hypomethylation Status of CpG Sites at the Promoter Region and Overexpression of the Human MDR1 Gene in Acute Myeloid Leukemias by Masaharu Nakayama, Morimasa.

RHD gene deletion occurred in the Rhesus box

Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib by Kathryn.

Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA by Rosanna Asselta, Valeria Rimoldi, Ilaria.

Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cells Youwen Yang, PhD, Hans Michael Haitchi, MD,

Frequent mutations in the ligand-binding domain of PML-RARα after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship.

by Cheng-Han Huang, Ying Chen, Marion E. Reid, and Christine Seidl

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy Yu-jin Qu, Jin-li Bai, Yan-yan.

A Common Genetic Polymorphism (46 C to T Substitution) in the 5′-Untranslated Region of the Coagulation Factor XII Gene Is Associated With Low Translation.

High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric.

by Wen-feng Xu, Zhi-wei Xie, Dominic W. Chung, and Earl W. Davie

by Sanjai Sharma, and Alan Lichtenstein

by Fawwaz Yassin, Sheldon P. Rothenberg, Sreedhar Rao, Marilyn M

Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen Aα-chain gene are not associated with the decay of the mutant.

by Bartlomiej Przychodzen, Andres Jerez, Kathryn Guinta, Mikkael A

by David M. Weinstock, Beth Elliott, and Maria Jasin

Herlitz Junctional Epidermolysis Bullosa: Novel and Recurrent Mutations in the LAMB3 Gene and the Population Carrier Frequency Aoi Nakano, Ellen Pfendner,

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenosis Type VI (Hers Disease) Barbara Burwinkel, Henk D. Bakker, Eliezer Herschkovitz,

The (4;11)(q21;p15) Translocation Fuses the NUP98 andRAP1GDS1 Genes and Is Recurrent in T-Cell Acute Lymphocytic Leukemia by Damian J. Hussey, Mario Nicola,

Undifferentiated Small Round Cell Sarcomas with Rare EWS Gene Fusions

A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote Daniel F. Wallace, James S. Dooley, Ann P.

Molecular Mechanisms of Junctional Epidermolysis Bullosa: Col15 Domain Mutations Decrease the Thermal Stability of Collagen XVII Laura Väisänen, Cristina.

Volume 84, Issue 3, Pages (February 1996)

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Congenital Insensitivity to Pain with Anhidrosis: Novel Mutations in the TRKA (NTRK1) Gene Encoding A High-Affinity Receptor for Nerve Growth Factor

Acquisition of Oncogenic Potential by RAR Chimeras in Acute Promyelocytic Leukemia through Formation of Homodimers Richard J Lin, Ronald M Evans Molecular.

Analysis of Rare APC Variants at the mRNA Level

Identification and Rescue of Splice Defects Caused by Two Neighboring Deep-Intronic ABCA4 Mutations Underlying Stargardt Disease Silvia Albert, Alejandro.

Peter Ianakiev, Michael W

Trans-Splicing to Spliceosomal U2 snRNA Suggests Disruption of Branch Site-U2 Pairing during Pre-mRNA Splicing Duncan J. Smith, Charles C. Query, Maria.

Identification and differential expression of human collagenase-3 mRNA species derived from internal deletion, alternative splicing, and different polyadenylation.

Supplemental Figure 3 A B C T-DNA 1 2 RGLG1 2329bp 3 T-DNA 1 2 RGLG2

Molecular Therapy - Nucleic Acids

Laminin-5 Mutational Analysis in an Italian Cohort of Patients with Junctional Epidermolysis Bullosa Patrizia Posteraro, Naomi De Luca, Guerrino Meneguzzi,

Andrew R. Bassett, Charlotte Tibbit, Chris P. Ponting, Ji-Long Liu

Haploinsufficiency for One COL3A1 Allele of Type III Procollagen Results in a Phenotype Similar to the Vascular Form of Ehlers-Danlos Syndrome, Ehlers-Danlos.

Imprinting at the SMPD1 Locus: Implications for Acid Sphingomyelinase–Deficient Niemann-Pick Disease Calogera M. Simonaro, Jae-Ho Park, Efrat Eliyahu,

Hiroaki Matsunami, Linda B Buck Cell

A Homozygous Nonsense Mutation in Type XVII Collagen Gene (COL17A1) Uncovers an Alternatively Spliced mRNA Accounting for an Unusually Mild Form of Non-Herlitz.

A Presenilin-1 Truncating Mutation Is Present in Two Cases with Autopsy-Confirmed Early-Onset Alzheimer Disease Carolyn Tysoe, Joanne Whittaker, John.

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Volume 58, Issue 2, Pages (August 2000)

Volume 25, Issue 2, Pages (February 2017)

APOE Gene Targeting (A) Schematic representation of the endogenous APOE locus, the gene targeting vector and the targeted APOE locus. The exons of the.

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Identification of FOXP2 Truncation as a Novel Cause of Developmental Speech and Language Deficits Kay D. MacDermot, Elena Bonora, Nuala Sykes, Anne-Marie.

Accurate, simple, and inexpensive assays to diagnose F8 gene inversion mutations in hemophilia A patients and carriers by Debargh Dutta, Devi Gunasekera,

Compound Heterozygosity for Novel Splice Site Mutations in the BPAG2/COL17A1 Gene Underlies Generalized Atrophic Benign Epidermolysis Bullosa Leena Pulkkinen,

Wook Lew Journal of Investigative Dermatology

Activation of MET by Gene Amplification or by Splice Mutations Deleting the Juxtamembrane Domain in Primary Resected Lung Cancers Ryoichi Onozato, MD,

The sh339 and qmc554 alleles of gfi1b.

Molecular Therapy - Nucleic Acids

Bart A. Jessen, Marjorie A. Phillips, Robert H. Rice

Expression of multiple forms of MEL1 gene products.

Two Exon-Skipping Mutations as the Molecular Basis of Succinic Semialdehyde Dehydrogenase Deficiency (4-Hydroxybutyric Aciduria) Ken L. Chambliss, Debra.

In vitro interaction domain mapping of pVHL and AUF1.

Hinrich Gronemeyer, Arthur Zelent Cancer Cell

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

Marc-André Langlois, Nan Sook Lee, John J Rossi, Jack Puymirat

K. Miura, M. Obama, K. Yun, H. Masuzaki, Y. Ikeda, S. Yoshimura, T

Presentation transcript:

Leukemic Cellular Retinoic Acid Resistance and Missense Mutations in the PML-RAR Fusion Gene After Relapse of Acute Promyelocytic Leukemia From Treatment With All-trans Retinoic Acid and Intensive Chemotherapy by Wei Ding, Yun-Ping Li, Lucio M. Nobile, George Grills, Ines Carrera, Elisabeth Paietta, Martin S. Tallman, Peter H. Wiernik, and Robert E. Gallagher Blood Volume 92(4):1172-1183 August 15, 1998 ©1998 by American Society of Hematology

Schematic structure of PML-RAR mRNA showing the major functional domains. Schematic structure of PML-RAR mRNA showing the major functional domains. The PML portion is hatched and the RAR portion is clear. Numbers in the boxes indicate exons. Vertical arrows indicate the positions of break/fusion sites in the translocated PML gene that result in the formation of three different forms of PML-RAR mRNA: S-, V-, and L-forms. Arrowheads show the sites of PCR primers used in this study. Primers used for screening of the PML region are shown beneath the schematic bar, whereas those for the RAR region are shown above it. The asterisks indicate the positions of base changes found in the PML-RAR allele, and the coding region amino acid changes are shown in expanded form below the schematic bar. The abbreviations are as follows: Pro, proline-rich domain; Cys, cysteine/histidine clusters; -Helix, -helical coiled-coil dimerization domain; B-F, B- to F-region of RAR; ZF, zinc-finger RING motif; BB1 and BB2, two B-boxes; DBD, DNA binding domain; DD, dimerization domain; LBD, ligand binding domain; AF-2, activator function-2 domain; AF-2 AD CORE, 7 amino acid long AF-2 activation domain; 3′-UT, 3′ untranslated region. Wei Ding et al. Blood 1998;92:1172-1183 ©1998 by American Society of Hematology

In vitro RA-induced differentiation of pretreatment and relapse APL cells from selected patients determined by the NBT test. In vitro RA-induced differentiation of pretreatment and relapse APL cells from selected patients determined by the NBT test. (A) Case no. 12; (B) case no. 9; (C) case no. 17; (D) case no. 14. (▪) pretreatment sample; (•) relapse sample. Case no. 12 only: (▴) primary DA refractoriness; (▾) postintravenous liposomal RA. Wei Ding et al. Blood 1998;92:1172-1183 ©1998 by American Society of Hematology

Comparison of the gel electrophoretic pattern of RT-PCR products from the pretreatment and relapse specimens of case no. 9. Comparison of the gel electrophoretic pattern of RT-PCR products from the pretreatment and relapse specimens of case no. 9. PCR amplification used primer pair I as described in the Materials and Methods. M1, Hae III-digested ΦX 174 DNA; M2, 100-bp size standard; H, HL-60 cell RNA; N, NB4 cell RNA; P, pretreatment RNA; R, relapse RNA. PCR band 1, full-length V-form with PML breaksite at nt 1685; band 2, full-length product of comigrating atypical isoforms with breaksites at nts 1576 and 1581; band 3, same as band 1 but lacking exon 5 due to alternative splicing; band 4, same as band 2 but lacking exon 5; band 5, isoform lacking exons 5 and 6 due to alternative splicing. Wei Ding et al. Blood 1998;92:1172-1183 ©1998 by American Society of Hematology

Automated DNA sequence analysis of PCR products from four APL cases with single nucleotide changes. Automated DNA sequence analysis of PCR products from four APL cases with single nucleotide changes. The upper panels show bi-allelic sequencing results for the pretreatment samples, which contain normal signals as indicated by the arrows in (A), (B), and (C), whereas (D) demonstrates a heterozygous pattern. The middle panels show heterozygous bi-allelic signals for the corresponding relapse samples. The lower panels show the results of nested, PML-RAR allele-specific amplification of PCR products from the relapse cases. (A) Case no. 9, T→C (Met→Thr). (B) Case no. 17, C→T (Arg→Trp). (C) Case no. 14, C→G (Leu→Val). (D) Case no. 2, C→T in 3′-UT region (illustrated from antisense strand sequence analysis, ie, shown as G→A; in the upper panel the heterozygotic mutant A appears on the shoulder of the normal G). Wei Ding et al. Blood 1998;92:1172-1183 ©1998 by American Society of Hematology