Multi-omics reveal immune microenvironment alterations in multiple myeloma and its precursor stages.

Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. In this study, we aim to systematically characterize the tumor immune microenvironment (TME) and the tumor-immune interactions from precursor stages, i.e.

DNA structural features and variability of complete MHC locus sequences.

The major histocompatibility (MHC) locus, also known as the Human Leukocyte Antigen (HLA) genes, is located on the short arm of chromosome 6, and contains three regions (Class I, Class II and Class III). This 5 Mbp locus is one of the most variable regions of the human genome, yet it also encodes a set of highly conserved and important proteins related to immunological response. Genetic variations in this region are responsible for more diseases than in the entire rest of the human genome.

Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis.

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients.

Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth.

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse.

BCMA- and CST6-specific CAR T cells lyse multiple myeloma cells and suppress murine osteolytic lesions.

We have previously demonstrated that cystatin E/M (CST6), which is elevated in a subset of patients with multiple myeloma (MM) lacking osteolytic lesions (OLs), suppresses MM bone disease by blocking osteoclast differentiation and function. CST6 is a secreted type 2 cystatin, a cysteine protease inhibitor that regulates lysosomal cysteine proteases and the asparaginyl endopeptidase legumain. Here, we developed B cell maturation antigen (BCMA) CST6 chimeric antigen receptor T cells (CAR-T cells), which lysed MM cells and released CST6 proteins.

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma.

Background: Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk-defining features. The authors report the prognostic value of del(1p13.3) by fluorescence in situ hybridization (FISH) at enrollment in subjects treated on total therapy clinical trials 2-6.

AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity.

Metabolic alterations are important cancer-associated features that allow cancer cell transformation and survival under stress conditions. Multiple myeloma (MM) plasma cells show increased glycolysis and oxidative phosphorylation (OXPHOS), which are characteristics associated with recurrent genetic aberrations that drive the proliferation and survival of MM cells. The protein kinase B/AKT acts as a central node in cellular metabolism and is constitutively active in MM cells.

TRIP13 modulates protein deubiquitination and accelerates tumor development and progression of B cell malignancies.

Multiple myeloma (MM), a terminally differentiated B cell malignancy, remains difficult to cure. Understanding the molecular mechanisms underlying the progression of MM may identify therapeutic targets and lead to a fundamental shift in treatment of the disease. Deubiquitination, like ubiquitination, is a highly regulated process, implicated in almost every cellular process.

Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?

Background: We hypothesized that disconcerting lymphedema rates in both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may be because of unrecognized vunerable variations in arm lymphatic drainage within the axilla. Axillary reverse mapping (ARM) facilitates identification and avoidance of arm lymphatics within the axilla and its use may reduce lymphedema.

Methods: This institutional review board-approved study from June 2007 to December 2013 involved patients undergoing SLNB with or without ALND, or ALND alone.

Axillary reverse mapping: five-year experience.

Background: We hypothesize that mapping the lymphatic drainage of the arm with blue dye (axillary reverse mapping [ARM]) during axillary lymphadenectomy decreases the likelihood of disruption of lymphatics and subsequent lymphedema.

Methods: This institutional review board-approved study involved 360 patients undergoing sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) from May 2006 to October 2011. Technetium sulfur colloid (4 mL) was injected subareolarly, and 5 mL of blue dye was injected subcutaneously in the volar surface ipsilateral upper extremity (ARM).

The CUBE technique: continuous ultrasound-guided breast excision.

Background: Margin negativity is a critical endpoint in breast-conserving surgery. Despite advances in technology, there is up to a 40 % positive margin rate in lumpectomy specimens, which results in a twofold increase in ipsilateral breast tumor recurrence. We have developed a new method for lumpectomy that could improve margin negativity.