did rockefeller found the american cancer society
I want a nation of workers." On her first trip to Iowa in September 2007, she thought she would only be there a few days and packed accordingly. "It was a great place to grow up." A heterogeneous response to 2-DG (half maximal effective concentrations [EC50s] ranging from 0.9 mM to >100 mM) was observed, which did not differ significantly between the BCL subtypes, although it is noteworthy that MM1.S (an HMCL) and Namalwa (a BLCL) showed a marked resistance (EC50 >100 mM) (Figure1B & supplemental Figure1B). NONE OF FAMILY ON SHIP $50,000 Fee Reported for Psychoanalyst Who Will See Herto Chicago Home", "MRS. H. F. M'CORMICK OBTAINS DIVORCE IN FIFTY MINUTES; John D. Rockefeller's Daughter Gains Decree for Desertion, Which Husband Admits. FOXO represses the expression of metabolic genes in MM cells. "My mission is to promote timely screenings," she says. This notion, in combination with our finding that MM cells display limited metabolic adaptability suggests that the FOXO-dependent regulation of metabolic features may represent an attractive therapeutic Achilles heel. According to the UAMS website, the "NCI Designation is a highly competitive assessment process during which cancer centers must demonstrate outstanding depth and breadth of high-quality cancer research and treatment." She was quoted as saying, "I married King Tutankhamen when I was only sixteen years old. Interestingly, our findings could be extended to patients with MM and have important prognostic implications. Now it seems that another iconic American institution has turned its back on the Sussexes: The Rockefeller family. Like a flash I recognized that chair. Gene expression profile (GEP) dataset E-TABM-113822 was obtained from the ArrayExpress archive, and datasets GSE6477,23 GSE2658,24,25 and GSE12094118 were obtained from the NCBI Gene Expression Omnibus database. "[16] She followed up in Time magazine by stating "My interest in reincarnation is of many years' standing. John D. Rockefeller (1839-1937), founder of the Standard Oil Company, became one of the world's wealthiest men and a major philanthropist. She knew something was wrong, so she planned to drive to Texarkana to see a doctor her family knew. doi: https://doi.org/10.1182/bloodadvances.2022007383. To investigate the effects of FOXO activation on the expression of genes involved in metabolism, gene expression data obtained from FOXO1- (LME-1) or FOXO3- (MM1.S and XG-3) deficient clones treated with MK2206 were investigated. ; Her Leadership of Chicago Society Unchallenged to the End", "Fowler McCormick Dies at 74; ExChairman of Harvester", "MRS. MAX OSER DIES ON COAST; Granddaughter of the Late John D. Rockefeller, Sister of Fowfer McCormick ", "MRS. OSER GOES TO MOTHER; Rides in Twentieth Century to Bedside of Mrs. McCormick", "The Aryan Christ: The Secret Life of Carl Jung - ResearchGate", "A Quirky Visionary: Edith Rockefeller McCormick Reigned as Queen of Chicago's Elite", "MRS. H.F. M'CORMICK BACK AFTER 8 YEARS; Rockefeller's Daughter Denies Planning Divorce Action Against International Harvester Head. "I was tired all of the time, but I was going nonstop, and I always have." After recovering, she moved back to Fayetteville, where she had always hoped to return, and began focusing on fundraising projects. Longtime friends are not surprised at Lavender's dedication to colorectal cancer awareness and prevention. Upon graduation, he moved his family to Texarkana, where he joined a local law firm. Upon graduation from high school, Lavender headed to the University of Arkansas at Fayetteville where she studied advertising and public relations. "It was coming here and feeling supported, and there wasn't a time that I have ever been scared.". In that respect, (combinatorial) targeting of signaling pathways that regulate metabolic plasticity may be a preferred approach, placing the AKT kinase in the limelight again, where the prevention of feedback regulation and/or activation of salvage pathways will be key for a successful therapeutic modality. Although novel treatment strategies have improved the prognosis and outcome of MM, most patients eventually relapse and become refractory to further treatment. This year, she is already at work on raising money and recruiting a team of walkers for the third annual walk, which starts at 8:30 a.m. Saturday at War Memorial Stadium in Little Rock. ROCKEFELLER JR. Edith was born on August 31, 1872 at her parents' home in Cleveland, Ohio. However, at high glucose uptake rates, the activation of glycolysis and decreased mitochondrial respiration results in more ATP production due to a more efficient cytoplasmic solvent capacity.40 Rapidly proliferating cells are characterized by a high glucose uptake capacity,41 which may explain the glycolytic phenotype of HMCLs. -actin served as a loading control. AKT inhibition suppresses glycolysis and OXPHOS in MM cells. SHE TESTIFIES IN COURT He Is Absent and Makes No Defense, Although Represented by Counsel. These results suggest that AKT kinase activity exerts its oncogenic function in MM by driving glycolysis and the TCA cycle, which is associated with aggressive disease. It was shown previously that AKT has a direct effect on metabolism by phosphorylating several metabolic enzymes, such as HK2,47 ACLY,48 and phosphofructokinase.49 Although this may also occur in MM cells, our results suggest that this is not the major mode of action by which AKT regulates the metabolic features of MM cells. SAID RICHES HURT CHILDREN Harold F. McCormick, Ex-Husband, Has Received $30,000 a Year Since Divorce. (C) Basal respiration and spare respiratory capacity in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) or untreated(red bars) for 20 hours. In high school, Lavender was very involved in "almost every activity," she says. Correspondence: Jeroen E.J. Activation of PI3K/AKT signaling is an established oncogenic feature of MM cells, sustaining several antiapoptotic and proliferative pathways. This document may not be reprinted without the express written permission of Northwest Arkansas Newspapers LLC. Nevertheless, the glycolytic reserve of the primary MM cells was limited and similar to that observed in the HMCLs. AKT prevents the metabolic shutdown of multiple myeloma cells by restricting FOXO. Search for other works by this author on: Metabolic signature identifies novel targets for drug resistance in multiple myeloma, Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib, On respiratory impairment in cancer cells, An HK2 antisense oligonucleotide induces synthetic lethality in HK1-HK2+ multiple myeloma, Cyclin D1 targets hexokinase 2 to control aerobic glycolysis in myeloma cells, Metabolic heterogeneity in human lung tumors, The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type, Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin, Bortezomib resistance in multiple myeloma is associated with increased serine synthesis, Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells, The AKT kinase is activated in multiple myeloma tumor cells, Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma, The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses, PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells, Loss of PTEN expression leading to high Akt activation in human multiple myelomas, AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma, Is Akt the Warburg kinase?-Akt-energy metabolism interactions and oncogenesis, The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism, Analysis of PTEN deletions and mutations in multiple myeloma, Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3, Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling, Prognostic value of cyclin D2 mRNA expression in newly diagnosed multiple myeloma treated with high-dose chemotherapy and tandem autologous stem cell transplantations, Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Mitochondrial spare respiratory capacity: Mechanisms, regulation, and significance in non-transformed and cancer cells, Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation, Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells, Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants, Galactose enhances oxidative metabolism and reveals mitochondrial dysfunction in human primary muscle cells, The role of FOXO in the regulation of metabolism, Avalidated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1, TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3, Metabolic effects of recurrent genetic aberrations in multiple myeloma, Lactate dehydrogenase production and release in a newly established human myeloma cell line, Lactate, a putative survival factor for myeloma cells, is incorporated by myeloma cells through monocarboxylate transporters 1, Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer, Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines, Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited, Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements, Characterization of MYC translocations in multiple myeloma cell lines, Regulation of cancer cell metabolism: oncogenic MYC in the drivers seat, Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1, Myc-induced proliferation and transformation require Akt-mediated phosphorylation of FoxO proteins, Akt stimulates aerobic glycolysis in cancer cells, Hexokinase-II positively regulates glucose starvation induced autophagy through TORC1 inhibition, The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes, Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis, FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells, Mitochondria define intestinal stem cell differentiation downstream of a FOXO/notch axis, FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression, FOXO3a-SIRT6 axis suppresses aerobic glycolysis in melanoma, Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration, 2023 by The American Society of Hematology. Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. Of note, galactose is oxidized to pyruvate, yielding all glycolysis intermediates, thus indicating that it is unlikely that cell death is caused by the lack of glycolysis-derived metabolites required for anabolic processes.30. In addition, we show that the LE glycolysis, LE TCA, and LE OXPHOS gene sets are significantly enriched in MMPCs from newly diagnosed patients (Figure5B) and patients with refractory/relapsed MM in comparison with those having healthy donor plasma cells, but not in those with monoclonal gammopathy of undetermined significance. "I love it to this day," she says. "It was the campaign part that was the fun part for me," she says. And she found out the hard way. "She is literally living proof that screening saves lives. Blood Adv 2023; 7 (9): 16971712. The full-text version of this article contains a data supplement. That's for another blog post but here is a quote from John D. Rockefeller that summarizes his vision for . MM cells are characterized by the high expression of lactate dehydrogenase,35-37 which catalyzes the conversion of pyruvate into lactate instead of into acetyl-CoA. "We would go to different countries.". "It was a wonderful experience being on the 'Hill,'" she says. Most recently, Lavender has been involved with the "Be a Part of the Cure Walk" hosted by the UAMS Winthrop P. Rockefeller Cancer Institute. Most well-known for his career in big oil and the petroleum sector, Rockefeller, at the time of his death, was estimated to be worth 300 to 400 billion dollars making him the "richest man in modern history." Like many people though of the time, his influence on medicine has had detrimental long-term negative effects on society as a whole. She was the fourth daughter of schoolteacher Laura Celestia "Cettie" Spelman (18391915) and Standard Oil co-founder John Davison Rockefeller. [13] He was given custody of their youngest daughter Mathilde so that she could marry Max Oser, a Swiss riding instructor. Black Americans are about 20% more likely to get colorectal cancer and about 40% more likely to die from it than other ethnic groups. Offsetting these medical advances, World War I killed 16.6 million people, including 6.8 million civilians. "She has a way of just making people's lives better," Merritt says. Mean values of 3 individual experiments are depicted. In February 1923, she received some minor press for claiming to be the reincarnation of the wife of King Tutankhamen, whose tomb had just been explored and was a popular topic. To assess whether the expression of FOXO-regulated metabolic genes is of prognostic importance for patients with MM, we investigated an extended GEP dataset obtained from patients with MM (n= 776), which includes survival data.22,25,33 First, the metabolic genes most strongly regulated by FOXO in MM were identified by performing an LE analysis on the GSEA data, in which AKT inhibitortreated control HMCL clones were compared with FOXO-deficient clones (Figure3A and supplemental Figure3A-C). Editha McCormick (19031904), who also died young. From this we conclude that AKT-mediated negative regulation of FOXO licenses the expression of glycolysis- and TCA-associated genes in MM but not in premalignant plasma cell disorders, most likely reflecting higher energetic demands due to the increased proliferation of MM cells. Edith Rockefeller McCormick (August 31, 1872 August 25, 1932) was an American socialite, daughter of Standard Oil co-founder John D. Rockefeller. She called her parents to say she wanted to come home to Texarkana to see a doctor. In 2016, Lavender caught the attention of Katie Couric, the former co-anchor of NBC's Today Show, who led a national colorectal cancer awareness campaign in the late 1990s after her husband, Jay Monahan, died from the disease at age 42. (B) Basal glycolysis in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) for 20 hours or untreated (red bars). Univariate analysis showed that LE glycolysis (high), LE TCA (high), and LE OXPHOS (high) represent adverse features for OS (hazard ratios 1.6-1.7) in conjunction with other well-known adverse factors (Figure6A). April 30, 2023 at 7:30 a.m. Betsy Lavender at the Winthrop Rockefeller Cancer Institute at UAMS. They lived on the Arkansas side, which she calls the "good side" of Texarkana. "Sometimes, I think it was better than any drug they could have given me," she says. Participants can choose to do a 1K or 5K route (both are wheelchair and stroller accessible). Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. Experimental details are provided in the supplemental Materials and Methods. I had sat in it many times. UAMS started the walk in 2021 to honor patients with all forms of cancer and raise money for cancer research. By the turn on the 20th century, he controlled 90% of all oil refineries in the U.S. through his oil company, Standard Oil, which was later on broken up to become Chevron, Exxon, Mobil etc. and G.H.K. MM cells show restricted glycolytic reserve and heterogeneous metabolic flexibility. (C) Seahorse XF mitochondrial stress test profiles of CTRL clones (left panels, n= 2), and FOXO KO clones (middle panels, n= 2) treated for 20 hours with 2.5 M MK2206 (blue lines) or left untreated (red lines). Similar to other cancer types, MM cells predominantly fulfill their energetic demands via glycolysis,2,3 a phenomenon known as the Warburg effect.4 In agreement, it was shown that the glycolysis rate-limiting enzyme, hexokinase II (HK2), is highly expressed in MM and is associated with poor prognosis.2,5,6. "It's awareness for the doctors out there that have people coming to them with issues to know that these people are not too young.". I was his first wife. Conflict-of-interest disclosure: The authors declare no competing financial interests. "We left on a Saturday morning and drove all day," she recalls. The American Cancer Society invests hundreds of millions of dollars every year to fight cancer on a global scale and has earned the public trust by demonstrating a history of careful and proven financial stewardship for over a century. The increased glycolytic rate seems counterintuitive because glycolysis yields far less ATP per glucose molecule than that in mitochondrial respiration. It was rumored that when this was whispered to her at the dinner table, she proceeded to merely nod her head and allowed the party to continue without incident. The R2 genomics analysis and visualization platform (http://r2.amc.nl) was used for k-means clustering based on the GEP data and survival analysis using the Kaplan-Meier method. [20][21] She and two of her children, John and Editha, are buried in Graceland Cemetery in Chicago. Licensed under, Copyright 2023 by American Society of Hematology, Supplemental Materials and Methods, Reference, Table, and Figures, https://doi.org/10.1182/bloodadvances.2022007383, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). (A) Immunoblot analysis of HK2 and PKM2 in LME-1, MM1.S, and LP-1 HMCLs treated overnight with 2.5 M MK2206 AKT inhibitor or left untreated. Protein expression of the glycolysis rate-limiting enzyme HK2 was decreased upon MK2206 treatment, whereas the effects on pyruvate kinase M2 (PKM2) were modest (Figure2A). In MM, AKT activation is primarily caused by growth factors in the bone marrow and the sporadic loss of phosphatase and tensin homolog expression.17,21. [11] She returned to America in 1921 after an eightyear stay. "I had no reason to believe I was sick," she says. They later moved to Chicago. As for cancer, oh yeah, the American Cancer Society was founded by none other than Rockefeller in 1913. In the summer after her junior year, she landed a coveted internship in Sen. Dale Bumpers' office in Washington. Multiple myeloma (MM) is a malignancy characterized by the clonal expansion of plasma cells in the bone marrow. She and Harold, along with other wealthy patrons, founded the Grand Opera Company, the first in Chicago, in 1909. "Betsy Lavender has been such a tireless warrior and powerful voice about the importance of early detection for colon cancer," Couric says. She also helped local candidates campaign, putting up yard signs and other tasks. Furthermore, AKT inhibition significantly decreased glycolysis, which required functional FOXO expression (Figure4B). Cell lines, cell culture conditions, and details on reagents are provided in the supplemental Materials and Methods. AKT signaling is an important driver of metabolism, either directly through the phosphorylation of key metabolic enzymes, or indirectly by controlling the expression of metabolic genes.20 The latter mainly involves the regulation of members of the FOXO TFs. Original data are available on request from the corresponding author, Jeroen E. J. Guikema (j.e.guikema@amsterdamumc.nl). However, the therapeutic targeting of metabolic enzymes may not be straightforward, given the many redundancies within and between metabolic pathways and the lack of truly specific inhibitors/therapeutic agents. ); grants or awards from the US Department of Defense, National Cancer Institute (R01 CA236814) (DoD; CA180190), the Myeloma Crowd Research Initiative award, and the Riney Family Multiple Myeloma Research Program Fund (F.Z. These alterations may result in metabolic dependencies that can be exploited for therapeutic purposes. Previous works by us and others have shown that AKT plays a pivotal role in the survival and growth of MM cells.13-18 We recently showed that AKT restrains the tumor-suppressive functions of forkhead box O (FOXO) transcription factors (TFs) in MM.18 Importantly, AKT is a central node in the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin pathway that connects proliferation, survival, and cellular metabolism and drives glycolysis.19,20 Activation of AKT is common in cancer, either by activating mutations or by growth factors provided by the tumor microenvironment. | (B) GSEA enrichment plots show enrichment of the FOXO-regulated LE glycolysis, LE TCA cycle, and LE OXPHOS gene sets (supplemental Table1) in MM plasma cells from newly diagnosed patients (MMPCs, n= 75) compared with plasma cells from healthy donors (n= 15). "It was a fabulous environment that day," Lavender says, noting that more than 1,000 people participated in 2022. Please read our Terms of Use or contact us. For the TCA cycle a >1.2-fold (FOXO-dependent) decrease in gene expression is indicated. Metabolic alterations are important cancer-associated features that allow cancer cell transformation and survival under stress conditions. After Barack Obama was elected president and Joe Biden became vice president, Lavender helped with inaugural festivities and then began coordinating travel arrangements for Biden and his family. Edith and her father had an often stormy relationship, where her extravagance would often conflict with his frugality. Moreover, glucose uptake did not decrease upon AKT inhibition, as shown by the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose uptake assay. To continue their mission today, Shah says the RF must "directly confront climate change". These results confirm that FOXO suppresses the expression of genes involved in metabolic pathways in patients with MM (Figure3E). Flexner is considered the 'father' of modern medical education. And she returned to working on campaigns when a friend ran for student body president. The plan fell through for undisclosed reasons in December 1922. After radiation, chemotherapy and surgery at UAMS, Lavender spent time recuperating in Texarkana at her family home. In agreement, the phosphorylation of FOXO1 (Thr24) and FOXO3 (Thr32), which mark their inactivation, followed a similar pattern (Figure1F). Her mother would play piano and they would all sing. To further assess metabolic adaptability, HMCLs were cultured for 4 days in a medium in which glucose was replaced with galactose. UAMS says the economic impact on Arkansas could be $72 million, with 1,500 new jobs created over five years. Mathilde and Max were married in London in April 1923. In 1913 JDR established the Rockefeller Foundation to "promote the well-being of mankind throughout the world." In keeping with this broad commitment, the foundation has given important global assistance to public health, medical education, improved food production, scientific advancement, social research, and the arts. Moreover, AKT kinase is a major driver of glycolysis, stimulating the switch from mitochondrial respiration to aerobic glycolysis.46, Our results show that metabolic modulation by DCA and galactose adaptation resulted in the activation of AKT in MM cells and a concomitant FOXO inactivation, suggesting that altered metabolic demands are relayed into the PI3K/AKT signaling pathway, likely representing feedback regulation. Tera Futrell Kesterson of Nashville in Howard County, who met Lavender in college as Chi Omega sorority sisters, says Lavender is a "great friend" to many and inspired others with her courage, especially during her recovery from colorectal cancer. His father, William Avery . She is especially interested in raising awareness. She and her husband Harold Fowler McCormick were prominent in Chicago society, supporting many causes, including the city's first opera company. This was the pivotal moment when the AMA was no longer about the medicine and the physicians, it became America's most profitable LOBBY group. [12], Edith and Harold were divorced in December 1921. Interestingly, the spare respiratory capacity and the maximum respiration increased in the majority of the HMCLs (5 out of 6) (Figure1D). In 1930, Edith had a growth removed from her breast and died of cancer two years later on August 25, 1932,[19] surrounded by her family. Means of 3 to 6 measurements are shown, andvalues are normalized to the untreated control condition and depicted as a dotted line (one-sample t test). Her brother was John Davison Rockefeller Jr. (18741960). (D) Fold change of ECAR, basal respiration, maximum respiration, and spare respiratory capacity (OCR) from a Seahorse XF mitochondrial stress test in HMCLs treated with DCA (25 mM for 20 hours) or cultured for 4 days in a galactose-containing medium (11.1 mM, no glucose). A biographer of her father, however, makes it clear that this could not have been true: at the time of her son's death, Edith was with him at the family estate, Kykuit, at Pocantico Hills, New York. She and her husband Harold Fowler McCormick were prominent in Chicago society, supporting many causes, including the citys first opera company. G protein-coupled receptors (GPCRs) modulate diverse cellular signaling pathways and are important drug targets. When evidence began to emerge that petroleum based medicine was causing cancer, Rockefeller founded the American Cancer Society, through which he suppressed that information. She was a member of both the Young Democrats group and the Teenage Republicans. These results suggest that AKT signaling might be a determinant of metabolic adaptability in MM cells. "I think attitude probably was most important to me," she says, adding that it is important never to give up and "to make the best of everything. For the glycolysis pathway, red, blue, and yellow symbols indicate >1.5-fold (FOXO-dependent) decrease in gene expression in LME-1, MM1.S, and XG-3, respectively. This result is surprising because it was previously shown that a shorter (36 kDa) MCL-1 isoform is required for normal mitochondrial bioenergetics in mouse embryonic fibroblasts.54 However, it is unlikely that the overexpression of the shorter MCL-1 isoform would rescue mitochondrial respiration because we found many OXPHOS-associated genes decreased in a FOXO-dependent fashion upon AKT inhibition. In addition, AKT kinase activity regulated mitochondrial respiration in MM (Figure2C, supplemental Figure2E-F). (E) OCR/ECAR ratios of HMCLs cultured for 4 days in a glucose-containing medium or in a galactose-containing, glucose-free medium. Enrichment plots for Reactome glycolysis, KEGG TCA cycle, and GSEA Hallmark_oxidative_phosphorylation gene sets are shown. LME-1 cells showed low OCR when only glucose was present, in contrast to MM1.S (supplemental Figure2G). 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. American Cancer Society - 1913 . Notably, there was no correlation between 2-DG sensitivity and metabolic function in the cell lines tested (Figure1C and supplemental Figure1C), suggesting that 2-DGdependent cell death involves a different mechanism, such as the induction of endoplasmic reticulum stress through the inhibition of N-glycosylation, as previously described.28. provided analytical support; J.D.S., T.C.A., and F.Z. On Saturday, Betsy Lavender will lead a team in the "Be a Part of the Cure Walk" hosted by the University of Arkansas for Medical Sciences' Winthrop P. Rockefeller Cancer Institute in Little Rock . Replacing glucose with galactose resulted in a significant increase in cell death in several HMCLs (LME-1, XG-3, and RPMI-8226), suggesting that these cell lines are unable to generate sufficient ATP from OXPHOS, thus indicating defective mitochondrial respiration and limited metabolic adaptability.