Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort

Phylogeography of the South China Field Mouse (Apodemus draco) on the Southeastern Tibetan Plateau Reveals High Genetic Diversity and Glacial Refugia

The southeastern margin of the Tibetan Plateau (SEMTP) is a particularly interesting region due to its topographic complexity and unique geologic history, but phylogeographic studies that focus on this region are rare. In this study, we investigated the phylogeography of the South China field mouse, Apodemus draco, in order to assess the role of geologic and climatic events on the Tibetan Plateau in shaping its genetic structure. We sequenced mitochondrial cytochrome b (cyt b) sequences in 103 individuals from 47 sampling sites. In addition, 23 cyt b sequences were collected from GenBank for analyses. Phylogenetic, demographic and landscape genetic methods were conducted. Seventy-six cyt b haplotypes were found and the genetic diversity was extremely high (π = 0.0368; h = 0.989). Five major evolutionary clades, based on geographic locations, were identified. Demographic analyses implied subclade 1A and subclade 1B experienced population expansions at about 0.052-0.013 Mya and 0.014-0.004 Mya, respectively. The divergence time analysis showed that the split between clade 1 and clade 2 occurred 0.26 Mya, which fell into the extensive glacial period (EGP, 0.5-0.17 Mya). The divergence times of other main clades (2.20-0.55 Mya) were congruent with the periods of the Qingzang Movement (3.6-1.7 Mya) and the Kun-Huang Movement (1.2-0.6 Mya), which were known as the most intense uplift events in the Tibetan Plateau. Our study supported the hypothesis that the SEMTP was a large late Pleistocene refugium, and further inferred that the Gongga Mountain Region and Hongya County were glacial refugia for A. draco in clade 1. We hypothesize that the evolutionary history of A. draco in the SEMTP primarily occurred in two stages. First, an initial divergence would have been shaped by uplift events of the Tibetan Plateau. Then, major glaciations in the Pleistocene added complexity to its demographic history and genetic structure

Infants Rely More on Gaze Cues From Own-Race Than Other-Race Adults for Learning Under Uncertainty

International audienceDifferential experience leads infants to have perceptual processing advantages for own- over other-race faces, but whether this experience has downstream consequences is unknown. Three experiments examined whether 7-month-olds (range = 5.9-8.5 months; N = 96) use gaze from own- versus other-race adults to anticipate events. When gaze predicted an event's occurrence with 100% reliability, 7-month-olds followed both adults equally; with 25% (chance) reliability, neither was followed. However, with 50% (uncertain) reliability, infants followed own- over other-race gaze. Differential face race experience may thus affect how infants use social cues from own- versus other-race adults for learning. Such findings suggest that infants integrate online statistical reliability information with prior knowledge of own versus other race to guide social interaction and learning

Concurrent Bone Marrow Acute Undifferentiated Leukemia and Mediastinal T‐Lymphoblastic Lymphoma With Identical SET::NUP214 Fusion and PHF6 and EZH2 Mutations

ABSTRACT Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic malignancies

Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins

Matrix mechanics controls cell fate by modulating the bonds between integrins and extracellular matrix (ECM) proteins. However, it remains unclear how fibronectin (FN), type 1 collagen, and their receptor integrin subtypes distinctly control force transmission to regulate focal adhesion kinase (FAK) activity, a crucial molecular signal governing cell adhesion/migration. Here we showed, using a genetically encoded FAK biosensor based on fluorescence resonance energy transfer, that FN-mediated FAK activation is dependent on the mechanical tension, which may expose its otherwise hidden FN synergy site to integrin α5. In sharp contrast, the ligation between the constitutively exposed binding motif of type 1 collagen and its receptor integrin α2 was surprisingly tension-independent to induce sufficient FAK activation. Although integrin α subunit determines mechanosensitivity, the ligation between α subunit and the ECM proteins converges at the integrin β1 activation to induce FAK activation. We further discovered that the interaction of the N-terminal protein 4.1/ezrin/redixin/moesin basic patch with phosphatidylinositol 4,5-biphosphate is crucial during cell adhesion to maintain the FAK activation from the inhibitory effect of nearby protein 4.1/ezrin/redixin/moesin acidic sites. Therefore, different ECM proteins either can transmit or can shield from mechanical forces to regulate cellular functions, with the accessibility of ECM binding motifs by their specific integrin α subunits determining the biophysical mechanisms of FAK activation during mechanotransduction