ALBERT

Beschreibung: Abstract 2187 Plasma cells, the terminal effectors of the B-cell lineage include both short- and long-lived cells. The latter persist for extended periods in the absence of cell division, supported in niche environments. No model system has successfully recapitulated the function of the niche to allow the in vitro generation of long-lived plasma cells. This limits investigation into the factors controlling and targeting plasma cell populations. Here we describe the generation of mature human plasma cells with extended lifespan from peripheral blood B-cells. Cell division accompanies phenotypic maturation between plasmablasts and plasma cells. These cells then persist in the absence of cell division, remaining functional and viable in extended culture, currently limited solely by elective termination. Extended survival is accompanied by maturation to a phenotype consistent with human bone marrow plasma cells. By establishing a set of conditions sufficient to allow the development and persistence of mature human plasma cells in vitro, we recapitulate the essential function of the plasma cell niche. We definitively link phenotypic maturation to lifespan and provide the first platform with which to explore and manipulate the full trajectory of human plasma cell differentiation. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 3442 Gains of 1q21 (CKS1B) in plasma cell neoplasms (PCNs) occur frequently and are generally thought to be indicative of an adverse prognosis. The International Myeloma Workshop Consensus Panel 2 (May 2011) found there is insufficient data to suggest routine use of 1q21 (CKS1B) in risk stratification of PCNs. This same Workshop confirmed that FISH testing in PCNs should be plasma cell (PC) specific. Despite this, many laboratories still perform conventional FISH (conv FISH) testing for PCNs primarily due to cost and labor constraints. This study had three objectives: 1) to examine the cytogenetic profile of patients with 1q21 abnormalities, 2) to observe if there was a difference between cytogenetic profiles and the incidence of each additional abnormality detected by cIg FISH vs. conv FISH, 3) to elucidate the significance of 1q21 in the prognosis of PCNs. The same probe set was used for both cIg and conv FISH: FGFR3/IGH [t(4;14)], IGH/MAF [t(14;16)], CCND1/IGH [t(11;14)], RB1/LAMP1 (13q14/13q34), TP53 [del(17)(p17.1)] and 1q21 (CKS1B). For conv FISH ≥200 nuclei/probe were scored. For cIg FISH 100 cIg+ cells were scored/probe and ≥25 cIg+ cells required for conclusive reporting. cIg FISH was performed on bone marrow aspirates in 276 cases (age range: 25–91 years); conv FISH 1007 cases (age range: 26–96 years) - all confirmed PCNs. For cIg FISH the %PC range was 0.3–95%; conv FISH 0.02–95%. With cIg FISH there were 246 (90%) abnormal, 14(5%) normal and 16 (5%) inconclusive results. Of the abnormal cases, 111 (45%) had gains of 1q21 (73 (66%) with 3 copies; 38 (34%) with ≥4 copies + [3+≥4 copies]), 127 (46%) had RB1 deletions (RB1−) or monosomy 13 (−13), and 77 (28%) had ‘other abnormalities' (no 1q21 or 13 abnormalities). For conv FISH there were 448 (44.5%) normal and 559 (55.5%) abnormal cases. Of the abnormal cases, 206 (20.5%) had gains of 1q21 (130 (63%) with 3 copies; 76 (37%) with ≥4 copies + [3+≥4 copies]), 240 (24%) RB1− or −13, and 221 (22%) ‘other abnormalities'. True amplification of 1q21 (CKS1B) [≥7–10 copies] was not observed by cIg or conv FISH. The detection rate (% cases) of each aberration occurring in the 111 1q21 positive cases detected by cIg FISH was: −13 31.9%, CCND1x3 23.9%, t(11;14) 10.9%, t(4;14) 9.4%, TP53− 6.9%, t(14;16) 6.5%, and RB1− 6.2%. For conv FISH it was: −13 8.5%, CCND1x3 6.8%, t(11;14) 2.9%, t(4;14) 2.5%, t(14;16) 1.9%, TP53− 1.8%, and RB1− 1.8%. Statistical analysis showed that the detection of additional aberrations in patients with 1q21 gains was significantly higher by cIg FISH compared to conv FISH (

Beschreibung: Verifying forecasts of rare events is challenging, in part because traditional performance measures degenerate to trivial values as events become rarer. The extreme dependency score was proposed recently as a nondegenerating measure for the quality of deterministic forecasts of rare binary events. This measure has some undesirable properties, including being both easy to hedge and dependent on the base rate. A symmetric extreme dependency score was also proposed recently, but this too is dependent on the base rate. These two scores and their properties are reviewed and the meanings of several properties, such as base-rate dependence and complement symmetry that have caused confusion are clarified. Two modified versions of the extreme dependency score, the extremal dependence index, and the symmetric extremal dependence index, are then proposed and are shown to overcome all of its shortcomings. The new measures are nondegenerating, base-rate independent, asymptotically equitable, harder to hedge, and have regular isopleths that correspond to symmetric and asymmetric relative operating characteristic curves.