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OwnerJacobus Johannes Van Dongen, Eduardus Maria Schuuring +11inventors
InventorsJacobus Johannes Van Dongen, Eduardus Maria Schuuring, Jesus San Miquel, Ramon Garzia Sanz, Antonio Parreira, John Smith, Frances Lavender, Gareth Morgan, Paul Anthony Evans, Michael Kneba, Michael Hummel, Elizabeth Macintyre, Christian Bastard
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The invention relates to PCR-based clonality studies for among others early diagnosis of lymphoproliferative disorders. Provided is a set of nucleic acid amplification primers comprising a forward primer, or a variant thereof, and a reverse primer, or a variant thereof, capable of amplifying a rearrangement selected from the group consisting of a VH-JH IGH rearrangement, a DH-JH IGH rearrangement, a VK-JK IGK rearrangement, a VK/intron-Kde IGK rearrangement, a Vλ-Jλ IGL rearrangement, a Vβ-Jβ TCRB rearrangement, a Dβ-Jβ TCRB rearrangement, a Vγ-Jγ TCRG rearrangement, a Vδ-Jδ TCRD rearrangement, a Dδ-Dδ TCRD rearrangement, a Dδ-Jδ TCRD rearrangement, a Vδ-Dδ TCRD rearrangement, or a translocation selected from t(11; 14)(BCL1-IGH) and t(14;18)(BCL2-IGH). The primers can be used in PCR-based clonality studies for early diagnosis of lymphoproliferative disorders and detection of minimal residual disease (MRD). Also provided is a kit comprising at least one set of primers of the invention.
A set of nucleic amplification primers capable of amplifying a VH-JH IGH rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the VH family primers shown in FIG. 3B, or a variant thereof, and wherein said reverse primer is the JH consensus primer shown in FIG. 3B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a DH-JH IGH rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the DH family primers shown in FIG. 4A, or a variant thereof, and wherein said reverse primer is the JH consensus primer shown in FIG. 4A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a VK-JK IGK rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the VK family primers shown in FIG. 5B, or a variant thereof, and wherein said reverse primer is a JK primer shown in FIG. 5B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a VK/intron-Kde IGK rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vκ primers or the INTR primer shown in FIG. 5B, or a variant thereof, and wherein said reverse primer is the Kde primer shown in FIG. 5B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Vλ-Jλ IGL rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vλ primers shown in FIG. 6B, or a variant thereof, and wherein said reverse primer is the Jλ primer shown in FIG. 6B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Vβ-Jβ TCRB rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vβ family primers shown in FIG. 7B, or a variant thereof, and wherein said reverse primer is selected from the JβA en JβB primers shown in FIG. 7B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Dβ-Jβ TCRB rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the DB primers shown in FIG. 7B, or a variant thereof, and wherein said reverse primer is selected from the JβA en JβB primers shown in FIG. 7B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Vγ-Jγ TCRG rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vγ family primers shown in FIG. 8B, or a variant thereof, and wherein said reverse primer is selected from the Jγ primers shown in FIG. 8B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Vδ-Jδ TCRD rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vδ primers shown in FIG. 9B, or a variant thereof, and wherein said reverse primer is selected from the Jδ primers shown in FIG. 9B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Dδ-Dδ TCRD rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is the Dδ2 primer shown in FIG. 9B, or a variant thereof, and wherein said reverse primer is the Dδ3 primer shown in FIG. 9B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Dδ-Jδ TCRD rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is the Dδ2 primer shown in FIG. 9B, or a variant thereof, and wherein said reverse primer is selected from the Jδ primers shown in FIG. 9B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a Vδ-Dδ TCRD rearrangement comprising a forward primer and a reverse primer, wherein said forward primer is selected from the Vδ primers shown in FIG. 9B, or a variant thereof, and wherein said reverse primer is the Dδ3 primer shown in FIG. 9B, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a chromosomal translocation (11;14)(BCL1-IGH) comprising a forward primer and a reverse primer, wherein said forward primer is the BCL1/MTC primer as shown in FIG. 10A, or a variant thereof, and wherein said reverse primer is the JH consensus primer shown in FIG. 10A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying a chromosomal translocation t(14;18)(BCL2-IGH), comprising a forward primer and a reverse primer, wherein said forward primer is selected from the MBR primers, the 3′MBR primers and the mcr primers shown in FIG. 11A, or a variant thereof, and wherein said reverse primer is the JH consensus primer shown in FIG. 11A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying the human TBXAS1 gene comprising a forward and a reverse primer, wherein said forward primer is the TBXAS1/X9U primer of FIG. 12A, or a variant thereof, and wherein said reverse primer is the TBXAS1/X9L primer of FIG. 12A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying the human recombination activating protein (RAG1) gene comprising a forward and a reverse primer, wherein said forward primer is the RAG1/X2U primer of FIG. 12A, or a variant thereof, and wherein said reverse primer is the RAG1/X2L primer of FIG. 12A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying human promyelocytic leukemia zinc finger protein (PLZF) comprising a forward and a reverse primer, wherein said forward primer is the PLZF/X1U primer of FIG. 12A, or a variant thereof, and wherein said reverse primer is the PLZF/X1L primer of FIG. 12A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying gene the human AF4 gene (Exon 3) comprising a forward and a reverse primer, wherein said forward primer is the AF4/X3U primer of FIG. 12A, or a variant thereof, and wherein said reverse primer is the AF4/X3L primer of FIG. 12A, or a variant thereof.
A set of nucleic amplification primers capable of amplifying gene the human AF4 gene (Exon11) comprising a forward and a reverse primer, wherein said forward primer is the AF4/X11U primer of FIG. 12A, or a variant thereof, and wherein said reverse primer is the AF4/X11L primer of FIG. 12A, or a variant thereof.
Dependencies are inferred from the claim text.