B-cell Lymphoma 6 (BCL6): From Master Regulator of Humoral Immunity to Oncogenic Driver in Pediatric Cancers.

B-cell lymphoma 6 (BCL6) is a protooncogene in adult and pediatric cancers, first identified in diffuse large B-cell lymphoma (DLBCL) where it acts as a repressor of the tumor suppressor TP53, conferring survival, protection, and maintenance of lymphoma cells. BCL6 expression in normal B cells is fundamental in the regulation of humoral immunity, via initiation and maintenance of the germinal centers (GC). Its role in B cells during the production of high affinity immunoglobins (that recognize and bind specific antigens) is believed to underpin its function as an oncogene. BCL6 is known to drive the self-renewal capacity of leukemia-initiating cells (LIC), with high BCL6 expression in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and glioblastoma (GBM) associated with disease progression and treatment resistance. The mechanisms underpinning BCL6-driven therapy resistance are yet to be uncovered; however, high activity is considered to confer poor prognosis in the clinical setting. BCL6's key binding partner, BCL6 corepressor (BCOR), is frequently mutated in pediatric cancers and appears to act in concert with BCL6. Using publicly available data, here we show that BCL6 is ubiquitously overexpressed in pediatric brain tumors, inversely to BCOR, highlighting the potential for targeting BCL6 in these often lethal and untreatable cancers. In this review, we summarize what is known of BCL6 (role, effect, mechanisms) in pediatric cancers, highlighting the two sides of BCL6 function, humoral immunity, and tumorigenesis, as well as to review BCL6 inhibitors and highlight areas of opportunity to improve the outcomes of patients with pediatric cancer.

A Novel Root-Knot Nematode Resistance QTL on Chromosome Vu01 in Cowpea.

The root-knot nematode (RKN) species Meloidogyne incognita and M. javanica cause substantial root system damage and suppress yield of susceptible cowpea cultivars. The narrow-based genetic resistance conferred by the Rk gene, present in some commercial cultivars, is not effective against Rk-virulent populations found in several cowpea production areas. The dynamics of virulence within RKN populations require a broadening of the genetic base of resistance in elite cowpea cultivars. As part of this goal, F1 and F2 populations from the cross CB46-Null (susceptible) x FN-2-9-04 (resistant) were phenotyped for M. javanica induced root-galling (RG) and egg-mass production (EM) in controlled growth chamber and greenhouse infection assays. In addition, F[Formula: see text] families of the same cross were phenotyped for RG on field sites infested with Rk-avirulent M. incognita and M. javanica The response of F1 to RG and EM indicated that resistance to RKN in FN-2-9-04 is partially dominant, as supported by the degree of dominance in the F2 and F[Formula: see text] populations. Two QTL associated with both RG and EM resistance were detected on chromosomes Vu01 and Vu04. The QTL on Vu01 was most effective against aggressive M. javanica, whereas both QTL were effective against avirulent M. incognita Allelism tests with CB46 x FN-2-9-04 progeny indicated that these parents share the same RKN resistance locus on Vu04, but the strong, broad-based resistance in FN-2-9-04 is conferred by the additive effect of the novel resistance QTL on Vu01. This novel resistance in FN-2-9-04 is an important resource for broadening RKN resistance in elite cowpea cultivars.

Broad-based root-knot nematode resistance identified in cowpea gene-pool two.

Cowpea (Vigna unguiculata L. Walp) is an affordable source of protein and strategic legume crop for food security in Africa and other developing regions; however, damage from infection by root-knot nematodes (RKN) suppresses cowpea yield. The deployment through breeding of resistance gene Rk in cowpea cultivars has provided protection to cowpea growers worldwide for many years. However, occurrence of more aggressive nematode isolates threatens the effectiveness of this monogenic resistance. A cowpea germplasm collection of 48 genotypes representing the cowpea gene-pool from Eastern and Southern Africa (cowpea has two major pools of genetic resources - Western Africa and Eastern/Southern Africa) was screened in replicated experiments under field, greenhouse and controlled-growth conditions to identify resistance to RKN, to determine the spectrum of resistance to RKN, the relative virulence (VI) among RKN species and isolates, and the relationship between root-galling (RG) and egg-mass production (EM). Analysis of variance of data for RG and EM per root system identified seven genotypes with broad-based resistance to Meloidogyne javanica (Mj), avirulent (Avr-Mi), and virulent (Mi) M. incognita isolates. Two of the 48 genotypes exhibited specific resistance to both Mi isolates. Most of the genotypes were resistant to Avr-Mi indicating predominance of Rk gene in the collection. Based on RG data, both Mj (VI = 50%) and Mi (VI = 42%) were fourfold more virulent than Avr-Mi (VI = 12%). Resistant genotypes had more effective resistance than the Rk-based resistance in cowpea genotype CB46 against Mj and Mi. Root-galling was correlated across isolates (Avr-Mi/Mj: r = 0.72; Mi/Mj: r = 0.98), and RG was correlated with EM (r = 0.60), indicating resistance to RG and EM is under control by the same genetic factors. These new sources of resistance identified in cowpea gene-pool two provide valuable target traits for breeders to improve cowpea production on RKN-infested fields.Cowpea (Vigna unguiculata L. Walp) is an affordable source of protein and strategic legume crop for food security in Africa and other developing regions; however, damage from infection by root-knot nematodes (RKN) suppresses cowpea yield. The deployment through breeding of resistance gene Rk in cowpea cultivars has provided protection to cowpea growers worldwide for many years. However, occurrence of more aggressive nematode isolates threatens the effectiveness of this monogenic resistance. A cowpea germplasm collection of 48 genotypes representing the cowpea gene-pool from Eastern and Southern Africa (cowpea has two major pools of genetic resources ­ Western Africa and Eastern/Southern Africa) was screened in replicated experiments under field, greenhouse and controlled-growth conditions to identify resistance to RKN, to determine the spectrum of resistance to RKN, the relative virulence (VI) among RKN species and isolates, and the relationship between root-galling (RG) and egg-mass production (EM). Analysis of variance of data for RG and EM per root system identified seven genotypes with broad-based resistance to Meloidogyne javanica (Mj), avirulent (Avr-Mi), and virulent (Mi) M. incognita isolates. Two of the 48 genotypes exhibited specific resistance to both Mi isolates. Most of the genotypes were resistant to Avr-Mi indicating predominance of Rk gene in the collection. Based on RG data, both Mj (VI = 50%) and Mi (VI = 42%) were fourfold more virulent than Avr-Mi (VI = 12%). Resistant genotypes had more effective resistance than the Rk-based resistance in cowpea genotype CB46 against Mj and Mi. Root-galling was correlated across isolates (Avr-Mi/Mj: r = 0.72; Mi/Mj: r = 0.98), and RG was correlated with EM (r = 0.60), indicating resistance to RG and EM is under control by the same genetic factors. These new sources of resistance identified in cowpea gene-pool two provide valuable target traits for breeders to improve cowpea production on RKN-infested fields.

A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).

KEY MESSAGE: Genome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance.

Inheritance and mapping of Mj-2, a new source of root-knot nematode (Meloidogyne javanica) resistance in carrot.

Root-knot nematodes limit carrot production around the world by inducing taproot forking and galling deformities that render carrots unmarketable. In warmer climates, Meloidogyne javanica and Meloidogyne incognita are most prevalent. In F2 and F3 progeny from the cross between an Asian carrot resistant to M. javanica, PI 652188, and a susceptible carrot, resistance response was incompletely dominant with a relatively high heritability (H (2) = 0.78) and provided evidence for a single gene, designated Mj-2, contributing to resistance. Molecular markers linked to the previously described root-knot nematode resistance gene, Mj-1 on chromosome 8 derived from "Brasilia," demonstrated that Mj-2 does not map to that same locus but is on the same chromosome.