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Leukemia and Lymphoma Awareness Month

Leukemia and lymphoma are the most common forms of blood cancer. Both diseases are the result of a malignant transformation of a lymphocyte precursor. Overall, lymphomas are more common than leukemias. Leukemia, however, is the most common childhood cancer. Chemotherapy is the most common form of treatment; others include radiation and stem cell transplant. Research has enabled scientists to focus on targeted drugs and immunotherapies for the treatment of patients who don’t respond to the standard treatments.

To bring attention to the Leukemia and Lymphoma Awareness Month in September, the cancer team at Nature Communications has curated a collections of the latest articles on these diseases and focused on translational biology research down to new therapies.

Leukemia

Transposable elements are a potential source of transcriptional regulators, but how these sequences contribute to oncogenesis remains poorly understood. Here, the authors identify endogenous retroviruses (ERVs) with acute myeloid leukemia (AML)-associated enhancer chromatin signatures, and provide evidence that ERV activation provides an additional layer of gene regulation in AML.

Article | Open Access | | Nature Communications

T-cell activation primarily occurs in the lymph nodes, highly organized and specialized secondary lymphoid organs. Here the authors show that the acidic extracellular pH in lymph node paracortical zones limits cytokine production by effector T-cells, but does not alter their activation by antigen-presenting cells.

Article | Open Access | | Nature Communications

Epigenetic reprogramming is a hallmark of cancer. Here the authors find that resetting primed human embryonic stem cells to naïve state results in the acquisition of a DNA methylation landscape that mirrors the cancer DNA methylome and provides evidence that the transition to naïve pluripotency and oncogenic transformation share common epigenetic trajectories.

Article | Open Access | | Nature Communications

The alternative splicing regulator MBNL1 is overexpressed in MLL-rearranged leukaemia. Here, the authors show that MBNL1-mediated alternative splicing leads to a specific splicing profile in MLL-rearranged leukaemia and loss or inhibition of MBNL1 impairs leukaemia development in vitro and in vivo.

Article | Open Access | | Nature Communications

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

Article | Open Access | | Nature Communications

There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.

Article | Open Access | | Nature Communications

Cancer cells can produce asparagine, yet both the regulation and biological functions of asparagine are unclear. Here the authors show that p53 suppresses asparagine synthesis and disrupts asparagine-aspartate homeostasis contributing to tumor growth inhibition, and that asparagine and aspartate modulates AMPK-mediated p53 activation by physically binding to and regulating LKB1.

Article | Open Access | | Nature Communications

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Article | Open Access | | Nature Communications

Melanosomes traffic along F-actin in melanocytes. Here, the authors show that Rab27a coordinates SPIRE/FMN actin assembly and MyoVa motor proteins to generate a cell-wide actin/myosin network that links melanosomes and allows the collective activity of these force generators to drive their traffic.

Article | Open Access | | Nature Communications

B-cell acute lymphoblastic leukaemia (B-ALL) is a common childhood cancer. Here, the authors conducted a meta-analysis with four genome-wide association studies, totalling 5,321 cases and 16,666 controls of European descent, identifying B-ALL risk loci, whose integration with epigenomic profiling indicates cell-cycle and B-cell development deregulation as central mechanisms in B-ALL susceptibility, often in a subtype-specific fashion.

Article | Open Access | | Nature Communications

Rapid and accurate detection of fusion genes is important in cancer diagnostics. Here, the authors demonstrate that targeted RNA sequencing provides fast, sensitive and quantitative gene fusion detection and overcomes the limitations of approaches currently in clinical use.

Article | Open Access | | Nature Communications

Resistance to chemotherapy is a serious issue that can be influenced by RNA epigenetics and chromatin structure. Here, the authors show in leukaemia cells that RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) mediate chromatin structures that can modulate 5-Azacitidine response and resistance.

Article | Open Access | | Nature Communications

Acute myeloid leukaemia (AML) affects people of all ages. Here, the authors model AML in vivo and demonstrate that the age of the cell of origin impacts leukaemia development and the genetic signature where adult cells of origin give rise exclusively to AML and young cells of origin give rise to myeloid, lymphoid or mixed phenotype acute leukaemia.

Article | Open Access | | Nature Communications

How leukaemia cells invade the bone marrow by outcompeting haematopoietic cells is still unclear. Here, the authors used detailed cell number measurements in conjunction with a dual pulse labelling method to determine proliferation rates and followed the in vivo dynamics of AML disease progression.

Article | Open Access | | Nature Communications

The Wnt pathway is one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL) and is activated in only a subset of patients; however, no universal drivers of the disease have been identified. Here the authors show that Notch2 and β-catenin pathways are the main drivers of the pro-survival bidirectional crosstalk between stromal cells and leukemic cells.

Article | Open Access | | Nature Communications

Lymphoma

Therapy-induced senescence reflects a biological effector principle that is underrecognized in lesion-focused cancer precision medicine. Here the authors utilize mouse lymphoma genetics to functionally dissect senescence and cross-species apply a novel senescence-based prognosticator to lymphoma patients.

Article | Open Access | | Nature Communications

Oncogene addiction is considered as a cancer cell-autonomous phenomenon, but can also influence the host immune system. Here the authors show that MYC-driven lymphomagenesis is associated with a block in the maturation and effector functions of natural killer cells as a mechanism of tumor escape from immunosurveillance.

Article | Open Access | | Nature Communications

Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.

Article | Open Access | | Nature Communications

TMBIM6, a member of the transmembrane BI-1 motif-containing family of proteins, is overexpressed in many cancer types. Here, the authors show that TMBIM6 regulates AKT activation through mTORC2 assembly and ribosome association and identify an antagonist of TMBIM6 with anti-tumor properties.

Article | Open Access | | Nature Communications

Nanoparticle-based strategies have been proposed to enhance the benefit of cancer immunotherapy. Here the authors show that a cancer vaccine based on metal organic frameworks-gated mesoporous silica nanoparticles for antigen and immune potentiators delivery boosts the therapeutic efficacy of low-dose anti-PD1.

Article | Open Access | | Nature Communications

Several different genetic strategies have been reported for the modification of polyketide synthases but the highly repetitive modular structure makes this difficult. Here the authors report on an adapted Cas9 reaction and Gibson assembly to edit a target region of the polyketide synthases gene in vitro.

Article | Open Access | | Nature Communications

Immunoglobulin (Ig) rearrangement and translocation information are usually obtained by targeted sequencing of the respective loci. Here, the authors present the IgCaller algorithm, which extracts Ig heavy and light chain genetic properties from short-read whole-genome sequencing results to provide a feasible alternative to direct sequencing.

Article | Open Access | | Nature Communications

As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing, identifying cancer patients who are at an increased risk of death from heart disease is important. Here the authors report on risk of death from heart diseases among more than 7.5 million cancer patients.

Article | Open Access | | Nature Communications

The relationship between DNA damage response (DDR) and regulation of the tolerance to glucose restriction is currently unclear. Here the authors reveal that maintaining a physiological level of histones by Rad53-Spt21 is necessary for glucose tolerance via multiple parallel pathways, including derepression of subtelomeric genes and acetyl-coA regulation by histone acetylation.

Article | Open Access | | Nature Communications

Here the authors show that stronger immune selection and immune editing in females and younger patients lead to the accumulation of poorly presented driver mutations in tumors. These results may explain why young and female patients are characterized by lower response rates to immune checkpoint blockade therapies.

Article | Open Access | | Nature Communications

Disease prognosis after infection with Kaposi’s sarcoma-associated herpesvirus and Epstein-Barr Virus is highly variable. Here the authors carry out epidemiological and genetic analysis of a Ugandan cohort and suggest complex interactions may influence pathogenesis and transmission.

Article | Open Access | | Nature Communications

Bryostatin 1 is a unique therapeutic lead, however its scarce natural sources have hampered its use in treatment of human disease. Here, the authors use a scalable synthesis of bryostatin 1 to make close-in analogs which potently induce increased cell surface expression holding potential for immunotherapy.

Article | Open Access | | Nature Communications

The tryptophan metabolite kynurenine is an endogenous ligand of the aryl hydrocarbon receptor (AHR). Here, the authors show that AHR targeting in IDO/TDO-expressing tumours counteracts a regulatory T cell/macrophage suppressive axis and synergizes with immune checkpoint blockade to hinder tumour growth.

Article | Open Access | | Nature Communications

Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

Article | Open Access | | Nature Communications

Metabolic rewiring of cancer cells can be driven by both extrinsic and intrinsic factors. Here the authors show that microenvironmental factors induce metabolic rewiring of B-cell lymphoma through activation of STAT3 and NF-ΚB resulting in upregulation of the aminotransferase GOT2 and glutamine addiction.

Article | Open Access | | Nature Communications

Evidence implicating cancer drivers can be sparse when limited to clonal events. Here, the authors present a retrovirus driven in vivo lymphomagenesis time course including hundreds of thousands of subclonal mutations and demonstrate the utility of these in mapping the selective forces affecting cancer gene loci, including negatively selected mutations.

Article | Open Access | | Nature Communications

T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

Article | Open Access | | Nature Communications