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Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance. 火上加油：谷氨酰胺代谢如何维持白血病的生长和抵抗。

BioMed (Basel, Switzerland) Pub Date : 2026-03-01 Epub Date: 2026-02-04 DOI: 10.3390/biomed6010007

Giovannino Silvestri

{"title":"Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance.","authors":"Giovannino Silvestri","doi":"10.3390/biomed6010007","DOIUrl":"10.3390/biomed6010007","url":null,"abstract":"Glutamine metabolism has emerged as one of the most critical bioenergetic and biosynthetic programs sustaining leukemic cell growth, survival, stemness and therapeutic resistance. In both acute and chronic leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), malignant cells display a strong dependency on extracellular glutamine to support mitochondrial respiration, anabolic biosynthesis and redox homeostasis. This dependency is reinforced by oncogenic signaling networks, post-transcriptional metabolic regulation and microenvironmental adaptation within the bone marrow niche. Therapeutic strategies targeting glutamine utilization, including glutaminase inhibition, transporter blockade and enzymatic glutamine depletion, have demonstrated robust antileukemic activity in preclinical models, and early clinical efforts have begun to explore glutamine-directed interventions in myeloid neoplasms. However, metabolic plasticity, microenvironment-derived nutrient buffering and systemic toxicity remain significant limitations to clinical translation. This review provides a detailed synthesis of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms enforcing glutamine addiction, the downstream functional consequences on proliferation, redox balance and leukemic stem cell biology, the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy.","PeriodicalId":521203,"journal":{"name":"BioMed (Basel, Switzerland)","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Primary Cutaneous Cribriform Apocrine Carcinoma: A Case Report and Narrative Review. 原发性皮肤筛状大汗腺癌1例报告及叙述回顾。

BioMed (Basel, Switzerland) Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.3390/biomed5040026

Robyn Okereke, Anthony Linfante

{"title":"Primary Cutaneous Cribriform Apocrine Carcinoma: A Case Report and Narrative Review.","authors":"Robyn Okereke, Anthony Linfante","doi":"10.3390/biomed5040026","DOIUrl":"10.3390/biomed5040026","url":null,"abstract":"Background and clinical significance: Primary Cutaneous Cribriform Apocrine Carcinoma (PCCAC) is a rare, inert low-grade cutaneous malignancy that is diagnosed on histopathologic assessment. PCCAC usually presents in middle-aged adults as a solitary, subcutaneous nodule on the extremities. Characterized by anastomosing tubules and solid/cribriform nests of atypical epithelial cells generating a sieve-like display, the tumor is a histopathological variant of apocrine metaplasia of the skin. PCCAC also follows characteristic staining patterns. It is important to distinguish PCCAC from other similar histological variants, which may hold more grievous indications.Case presentation: A 47-year-old female presented with an enlarging, itchy growth of several months on her back. On physical exam, an indurated pink, nontender papule of 8 mm on the left lateral side wall was noted. Histopathology demonstrated a well-circumscribed, pandermal tumor composed of anastomosing solid and cribriform nests, tubules, and cords of mildly atypical, eosinophilic epithelial cells forming a glandular lumina. An immunohistochemical study revealed the tumoral epithelium to express CK7, CK5/6, BER-EP4, CD117 (C-kit), and S100. Positive EMA and CEA staining highlighted intratumoral glandular ductal differentiation and apocrine secretion. Immunohistochemical stains for CK20, GATA-3, and p63 were negative.Conclusions: We present this case to distinguish the histological attributes of PCCAC and help differentiate it from more concerning visceral metastatic malignancies. We follow with a narrative review of the histopathologic differential for PCCAC and feature reconciliation of corresponding staining patterns reported in the literature.","PeriodicalId":521203,"journal":{"name":"BioMed (Basel, Switzerland)","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0