Abstract: In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

Abstract: In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.

Abstract: 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 V?-J? IGL rearrangement, a V?-J? TCRB rearrangement, a D?-J? TCRB rearrangement, a V?-J? TCRG rearrangement, a V?-J? TCRD rearrangement, a D?-D? TCRD rearrangement, a D?-J? TCRD rearrangement, a V?-D? 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.

Abstract: 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-J? IGK rearrangement, a VK/intron-Kde IGK rearrangement, a V?-J? IGL rearrangement, a V?-J? TCRB rearrangement, a D?-J? TCRB rearrangement, a V?-J? TCRG rearrangement, a V?-J? TCRD rearrangement, a D?-D? TCRD rearrangement, a D?-J? TCRD rearrangement, a V?-D? 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.

Abstract: 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 V?-J? IGL rearrangement, a V?-J? TCRB rearrangement, a D?-J? TCRB rearrangement, a V?-J? TCRG rearrangement, a V?-J? TCRD rearrangement, a D?-D? TCRD rearrangement, a D?-J? TCRD rearrangement, a V?-D? 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.

Abstract: 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 V?-J? IGL rearrangement, a V?-J? TCRB rearrangement, a D?-J? TCRB rearrangement, a V?-J? TCRG rearrangement, a V?-J? TCRD rearrangement, a D?-D? TCRD rearrangement, a D?-J? TCRD rearrangement, a V?-D? 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.

Abstract: Methods for determining a prognosis in multiple myeloma are disclosed, and in particular to methods that are capable of identifying patients with a poor prognosis and/or for determining the likelihood of a patient responding to a particular treatment. The methods identify myeloma samples having homozygous deletions in cell death genes, with dysregulated expression of 97 cell death genes forming a cell death expression signature, which is associated with poor prognosis in multiple myeloma. In a preferred aspect, three gene pairs, were found to provide a prognostic a “six gene signature” based on BUB1B and HDAC3; CDC2 and FIS1; and RAD21 and ITM2B (high expressors and low expressors respectively).