← Back to all signals
RESEARCH PAPER ANALYSIS

Activation of nemo-like kinase in diamond blackfan anemia suppresses early erythropoiesis by preventing mitochondrial biogenesis.

AI interpretation is pending for this paper.

Open original publication →
PMID38992436
JournalThe Journal of biological chemistry
Publication Date2024-07-09
Ingested2026-08-02 12:02 AM
EXECUTIVE SUMMARY

What the AI sees

Not AI summarized yet.

WHY IT MATTERS

Research significance

Pending deeper interpretation.

ABSTRACT

Source abstract

Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown. Here we report that activated NLK suppresses the critical upregulation of mitochondrial biogenesis required in early erythropoiesis. During normal erythropoiesis, mTORC1 facilitates the translational upregulation of Transcription factor A, mitochondrial (TFAM), and Prohibin 2 (PHB2) to increase mitochondrial biogenesis. In our models of DBA, active NLK phosphorylates the regulatory component of mTORC1, thereby suppressing mTORC1 activity and preventing mTORC1-mediated TFAM and PHB2 upregulation and subsequent mitochondrial biogenesis. Improvement of erythropoiesis that accompanies NLK inhibition is negated when TFAM and PHB2 upregulation is prevented. These data demonstrate that a significant contribution of NLK on the pathogenesis of DBA is through loss of mitochondrial biogenesis.

SUPPORTING PAPER SET

32 more papers to review

Ranked by current scoring engine
1 Inverted Meckel's diverticulum in adults: two case reports and a systematic review. BMC gastroenterology 73.9 2 Torsion and infarction of a large pediatric mesenteric inflammatory myofibroblastic tumor: a case report. Journal of medical case reports 47.5 3 Preoperative Chemotherapy and Its Efficacy in Pediatric Wilms Tumor: A Systematic Review of Randomized Controlled Trials. Cureus 84.94 4 Fear of disease progression in primary caregivers of children with malignant solid tumors: a latent profile analysis. BMC psychology 66.9 5 Protracted copy number alteration evolution in Barrett's oesophagus leading to oesophageal cancer. medRxiv : the preprint server for health sciences 56.0 6 Editorial: The expanding spectrum of hemophagocytic lymphohistiocytosis: pathogenic mechanisms and therapeutic implications. Frontiers in immunology 33.09 7 DNA methylation profiling reveals novel rhabdomyosarcoma subsets with distinct histologic, genetic and clinical properties. medRxiv : the preprint server for health sciences 57.5 8 Brain microvascular endothelial cell dysfunction during Plasmodium infection does not result from astrocyte-derived wingless-related integration site (Wnt)7a deficiency. bioRxiv : the preprint server for biology 50.9 9 The role of microRNAs in neuroblastoma cell differentiation and their therapeutic potential: a systematic review. Frontiers in oncology 79.54 10 Temporal clinical trajectories and Day+14 landmark stratification of infection risk after CD19 CAR T-cell therapy. Frontiers in cellular and infection microbiology 71.52 11 Co-creating the EndoWatch - a smart wearable device for the management of hypothalamic dysfunction in pediatric brain tumor survivors: a pilot study. Frontiers in endocrinology 69.4 12 Ginsenoside RK3 suppresses osteosarcoma via PRMT5/GPX4-ferroptosis axis and enhances doxorubicin chemosensitivity. Frontiers in pharmacology 59.5 13 Age-dependent differences in SARS-CoV-2 entry-factor expression and innate immune responses between pediatric and adult liver organoids. Frontiers in public health 52.62 14 Health beliefs and parental responses to human papillomavirus vaccination in the Middle East: a theory-informed narrative synthesis guided by the health belief model. Frontiers in public health 81.12 15 Diagnostic potential of Aldo-keto reductase 1B10 in pediatric hepatic malignancies: a narrative, hypothesis-generating translational review based on adult evidence and future research directions. Frontiers in medicine 60.5 16 Mucormycosis beyond the classic host: a case series and narrative literature review from a tertiary Greek hospital. Frontiers in fungal biology 60.5 17 Incidence and mortality of breast cancer among adolescent and young adult women worldwide in 2022 and projections for 2040: Implications for surgery. Breast (Edinburgh, Scotland) 57.5 18 Dynamic Radiologic Severity Index is associated with antifungal treatment but does not independently predict initiation in pediatric acute lymphoblastic leukemia with post-chemotherapy pneumonia. Translational pediatrics 75.18 19 Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)-like spectrum with a unique NRAS c.182A>G (p.Q61R) variant: a case report. Translational pediatrics 55.2 20 Predictive value of novel inflammatory markers for post-infectious pulmonary embolism in children. Translational pediatrics 61.2 21 Persistent cerebrospinal fluid tumor cells during transient radiographic response in bilateral retinoblastoma with central nervous system involvement: a pediatric case report. Translational pediatrics 57.42 22 Risk-adapted radiotherapy in pediatric neuroblastoma: current evidence, controversies, and future directions-a narrative review. Translational pediatrics 70.44 23 Identification of amino acid metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical drug treatment in osteosarcoma. Translational pediatrics 74.9 24 Hepatic arterial infusion chemotherapy in combination with immune checkpoint inhibitors and targeted therapy for advanced intrahepatic cholangiocarcinoma. Journal of gastrointestinal oncology 77.18 25 Early on-treatment alpha-fetoprotein and des-gamma-carboxy prothrombin responses are associated with outcomes in unresectable hepatocellular carcinoma receiving transarterial chemoembolization, tyrosine kinase inhibitors and programmed cell death protein-1 inhibitors. Journal of gastrointestinal oncology 75.22 26 Nephrogenic adenoma of the bladder: a case report and review of the literature. Translational andrology and urology 53.4 27 Congenital adrenal hyperplasia combined with a huge adrenal myelolipoma of the unilateral adrenal gland in a 51-year-old female: a case report. Translational andrology and urology 54.3 28 Clinicogenomic characterization and targeted therapy efficacy in Chinese patients with NTRK fusion-positive thyroid cancer: a preliminary retrospective cohort study. Translational cancer research 81.02 29 Real-world efficacy and safety of blinatumomab across three clinical settings in pediatric B-cell acute lymphoblastic leukemia: a single-center retrospective cohort study. Translational cancer research 78.4 30 Telangiectatic Osteosarcoma Arising in a Treated Unicameral Bone Cyst of the Proximal Humerus: A Case Report. Journal of orthopaedic case reports 52.3 31 Multimodal Management of an Aggressive Vertebral Hemangioma in a Child with Neurological Deficit: A Case Report with 5-Year Follow-Up. Journal of orthopaedic case reports 57.0 32 Chernobyl Papillary Thyroid Carcinoma Reveals a Complex Interplay between Environmental Exposures and Lead Genetic Variants Predisposing to Thyroid Cancer. Environmental health perspectives 68.7
PATIENT-FRIENDLY SUMMARY

Activation of nemo-like kinase in diamond blackfan anemia suppresses early erythropoiesis by preventing mitochondrial biogenesis.

For education only—not personal medical advice.

Before you continue

AI-assisted research information

Neurocompute uses AI to summarize scientific papers, interpret research signals, and suggest relevant reference links. AI-generated content can be incomplete, misleading, or wrong, and generated links may be irrelevant or unavailable.

Our reviewed outputs have performed strongly to date, but past accuracy is not a guarantee. Verify summaries, scores, claims, and links against the original publication before relying on them.

This platform is for research and education only. It does not provide medical advice, diagnosis, treatment recommendations, or clinical guidance.

Pediatric cancer research intelligence graphic
PEDIATRIC CANCER VISUAL SYSTEM

Open the Research Intelligence Map

Explore the active pediatric oncology analysis view.

Expand Intelligence View →
Full Pediatric cancer research intelligence graphic