Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

In the present paper, we report on the use of the heteroduplex PCR technique to detect the presence of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) in the apheresis products of patients with multiple myeloma (MM) undergoing autologous peripheral blood stem cell (APBSC) transplantation. Twenty-three out of 31 MM patients undergoing APBSC transplantation with VDJH segments clonally rearranged detected at diagnosis were included in the study. Samples of the apheresis products were PCR amplified using JH and VH (FRIII and FRII) consensus primers and subsequently analyzed with the heteroduplex technique, and compared with those obtained at diagnosis. 52% of cases yielded positive results (presence of clonally rearranged VDJH segments in at least one apheresis). The presence of positive results in the apheresis products was not related to any pretransplant characteristics with the exception of response status at transplant. Thus, while no one patient with positive apheresis products was in complete remission (CR), negative immunofixation, before the transplant, five cases (46%) with negative apheresis were already in CR at transplant (P = 0.01). The remaining six cases with heteroduplex PCR negative apheresis were in partial remission before transplant. Patients with clonally free products were more likely to obtain CR following transplant (64% vs 17%, P= 0.02) and a longer progression-free survival, (40 months in patients transplanted with polyclonal products vs 20 with monoclonal ones, P = 0.03). These results were consistent when the overall survival was considered, since it was better in those patients with negative apheresis than it was in those with positive (83% vs 36% at 5 years from diagnosis, P= 0.01). These findings indicate that the presence of clonality rearranged VDJH segments is related to the response and outcome in MM transplanted patients.

Beamforming and interference cancellation in D2D communication underlaying cellular networks

This paper presents an analytical performance investigation of both beamforming (BF) and interference cancellation (IC) strategies for a device-to-device (D2D) communication system underlaying a cellular network with an M-antenna base station (BS). We first derive new closed-form expressions for the ergodic achievable rate for BF and IC precoding strategies with quantized channel state information (CSI), as well as, perfect CSI. Then, novel lower and upper bounds are derived which apply for an arbitrary number of antennas and are shown to be sufficiently tight to the Monte-Carlo results. Based on these results, we examine in detail three important special cases including: high signal-to-noise ratio (SNR), weak interference between cellular link and D2D link, and BS equipped with a large number of antennas. We also derive asymptotic expressions for the ergodic achievable rate for these scenarios. Based on these results, we obtain valuable insights into the impact of the system parameters, such as the number of antennas, SNR and the interference for each link. In particular, we show that an irreducible saturation point exists in the high SNR regime, while the ergodic rate under IC strategy is verified to be always better than that under BF strategy. We also reveal that the ergodic achievable rate under perfect CSI scales as log2M, whilst it reaches a ceiling with quantized CSI.

Beamforming and interference cancellation schemes for D2D communications

We investigate device-to-device (D2D) communication underlaying cellular networks with M-antenna base stations. We consider both beamforming (BF) and interference cancellation (IC) strategies under quantized channel state information (CSI), as well as, perfect CSI. We derive tight closed-form approximations of the ergodic achievable rate which hold for arbitrary transmit power, location of users and number of antennas. Based on these approximations, we derive insightful asymptotic expressions for three special cases namely high signal-to-noise (SNR), weak interference, and large M. In particular, we show that in the high SNR regime a ceiling effect exists which depends on the received signal-to-interference ratio and the number of antennas. Moreover, the achievable rate scales logarithmically with M. The ergodic achievable rate is shown to scale logarithmically with SNR and the antenna number in the weak interference case. When the BS is equipped with large number of antennas, we find that the ergodic achievable rate under quantized CSI reaches a saturated value, whilst it scales as log2M under perfect CSI.

Secure Multiple Amplify-and-Forward Relaying with Co-Channel Interference

We investigate the impact of co-channel interference on the security performance of multiple amplify-and-forward (AF) relaying networks, where N intermediate AF relays assist the data transmission from the source to the destination. The relays are corrupted by multiple co-channel interferers, and the information transmitted from the relays to destination can be overheard by the eavesdropper. In order to deal with the interference and wiretap, the best out of N relays is selected for security enhancement. To this end, we derive a novel lower bound on the secrecy outage probability (SOP), which is then utilized to present two best relay selection criteria, based on the instantaneous and statistical channel information of the interfering links. For these criteria and the conventional maxmin criterion, we quantify the impact of co-channel interference and relay selection by deriving the lower bound on the SOP. Furthermore, we derive the asymptotic SOP for each criterion, to explicitly reveal the impact of transmit power allocation among interferers on the secrecy performance, which offers valuable insights into practical design. We demonstrate that all selection criteria achieve full secrecy diversity order N, while the proposed in this paper two criteria outperform the conventional max-min scheme. 

An Efficient Precoder Design for Multiuser MIMO Cognitive Radio Networks with Interference Constraints

We consider a linear precoder design for an underlay cognitive radio multiple-input multiple-output broadcast channel, where the secondary system consisting of a secondary base-station (BS) and a group of secondary users (SUs) is allowed to share the same spectrum with the primary system. All the transceivers are equipped with multiple antennas, each of which has its own maximum power constraint. Assuming zero-forcing method to eliminate the multiuser interference, we study the sum rate maximization problem for the secondary system subject to both per-antenna power constraints at the secondary BS and the interference power constraints at the primary users. The problem of interest differs from the ones studied previously that often assumed a sum power constraint and/or single antenna employed at either both the primary and secondary receivers or the primary receivers. To develop an efficient numerical algorithm, we first invoke the rank relaxation method to transform the considered problem into a convex-concave problem based on a downlink-uplink result. We then propose a barrier interior-point method to solve the resulting saddle point problem. In particular, in each iteration of the proposed method we find the Newton step by solving a system of discrete-time Sylvester equations, which help reduce the complexity significantly, compared to the conventional method. Simulation results are provided to demonstrate fast convergence and effectiveness of the proposed algorithm.