{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:22:32Z","timestamp":1780100552573,"version":"3.54.0"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Malattie del Sangue (FMS) Onlus"},{"name":"Villaggio Amico S.r.l."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study aimed to investigate the causes of continuous deep fluctuations in the absolute lymphocyte count (ALC) in an untreated patient with Chronic Lymphocytic Leukemia (CLL), who has had a favorable prognosis since the time of diagnosis. Up until now, the patient has voluntarily chosen to adopt a predominantly vegetarian and fruitarian diet, along with prolonged periods of total fasting (ranging from 4 to 39 days) each year. Materials and Methods: For this purpose, we decided to analyze the whole transcriptome profiling of peripheral blood (PB) CD19+ cells from the patient (#1) at different time-points vs. the same cells of five other untreated CLL patients who followed a varied diet. Consequently, the CLL patients were categorized as follows: the 1st group comprised patient #1 at 20 different time-points (16 time-points during nutrition and 4 time-points during fasting), whereas the 2nd group included only one time point for each of the patients (#2, #3, #4, #5, and #6) as they followed a varied diet. We performed microarray experiments using a powerful tool, the Affymetrix Human Clariom\u2122 D Pico Assay, to generate high-fidelity biomarker signatures. Statistical analysis was employed to identify differentially expressed genes and to perform sample clustering. Results: The lymphocytosis trend in patient #1 showed recurring fluctuations since the time of diagnosis. Interestingly, we observed that approximately 4\u20136 weeks after the conclusion of fasting periods, the absolute lymphocyte count was reduced by about half. The gene expression profiling analysis revealed that nine genes were statistically differently expressed between the 1st group and the 2nd group. Specifically, IGLC3, RPS26, CHPT1, and PCDH9 were under expressed in the 1st group compared to the 2nd group of CLL patients. Conversely, IGHV3-43, IGKV3D-20, PLEKHA1, CYBB, and GABRB2 were over-expressed in the 1st group when compared to the 2nd group of CLL patients. Furthermore, clustering analysis validated that all the samples from patient #1 clustered together, showing clear separation from the samples of the other CLL patients. Conclusions: This study unveiled a small gene expression signature consisting of nine genes that distinguished an untreated CLL patient who followed prolonged periods of total fasting, maintaining a gradual growth trend of lymphocytosis, compared to five untreated CLL patients with a varied diet. Future investigations focusing on patient #1 could potentially shed light on the role of prolonged periodic fasting and the implication of this specific gene signature in sustaining the lymphocytosis trend and the favorable course of the disease.<\/jats:p>","DOI":"10.3390\/medicina59081405","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:06:44Z","timestamp":1690880804000},"page":"1405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Nine-Gene Expression Signature Distinguished a Patient with Chronic Lymphocytic Leukemia Who Underwent Prolonged Periodic Fasting"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-8391","authenticated-orcid":false,"given":"Luca Emanuele","family":"Bossi","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-0499","authenticated-orcid":false,"given":"Cassandra","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-2968","authenticated-orcid":false,"given":"Alessandra","family":"Trojani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostina","family":"Melluso","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-4688","authenticated-orcid":false,"given":"Barbara","family":"Di Camillo","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padova, 35020 Padua, Italy"},{"name":"Department of Comparative Biomedicine and Food Science, University of Padova, 35020 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-3474","authenticated-orcid":false,"given":"Alessandro","family":"Beghini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20146 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Maria","family":"Sarnataro","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-2623","authenticated-orcid":false,"given":"Roberto","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ajh.26367","article-title":"Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures","volume":"96","author":"Hallek","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16096","DOI":"10.1038\/nrdp.2016.96","article-title":"Chronic lymphocytic leukaemia","volume":"3","author":"Kipps","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","unstructured":"Montague, A.M., and Pathak, S. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/sj.leu.2403707","article-title":"Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia","volume":"19","author":"Schroers","year":"2005","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1182\/blood.V46.2.219.219","article-title":"Clinical staging of chronic lymphocytic leukemia","volume":"46","author":"Rai","year":"1975","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V","article-title":"A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis","volume":"48","author":"Binet","year":"1981","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100930","DOI":"10.1016\/j.blre.2022.100930","article-title":"CLL update 2022: A continuing evolution in care","volume":"54","author":"Kay","year":"2022","journal-title":"Blood Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1136\/jclinpath-2018-205622","article-title":"Relevance of TP53 for CLL diagnostics","volume":"72","author":"Catherwood","year":"2019","journal-title":"J. Clin. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"a035220","DOI":"10.1101\/cshperspect.a035220","article-title":"Chronic Lymphocytic Leukemia","volume":"11","author":"Chiorazzi","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41375-022-01802-y","article-title":"Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: A study by ERIC in HARMONY","volume":"37","author":"Mansouri","year":"2023","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-pathol-020712-163955","article-title":"The pathogenesis of chronic lymphocytic leukemia","volume":"9","author":"Zhang","year":"2014","journal-title":"Annu. Rev. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5763","DOI":"10.1182\/bloodadvances.2022007508","article-title":"A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression","volume":"6","author":"Abrisqueta","year":"2022","journal-title":"Blood Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/CBM-2012-0259","article-title":"Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia","volume":"11","author":"Trojani","year":"2011","journal-title":"Cancer Biomark."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.32471\/exp-oncology.2312-8852.vol-41-no-1.12391","article-title":"Analysis of LPL gene expression in patients with chronic lymphocytic leukemia","volume":"41","author":"Bilous","year":"2019","journal-title":"Exp. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1182\/blood.2020009960","article-title":"ZAP-70 constitutively regulates gene expression and protein synthesis in chronic lymphocytic leukemia","volume":"137","author":"Chen","year":"2021","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJM200012283432602","article-title":"Genomic aberrations and survival in chronic lymphocytic leukemia","volume":"343","author":"Stilgenbauer","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1111\/liv.14167","article-title":"Serum coding and non-coding RNAs as biomarkers of NAFLD and fibrosis severity","volume":"39","author":"Scamporrino","year":"2019","journal-title":"Liver Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1073\/pnas.87.5.1663","article-title":"Amplified RNA synthesized from limited quantities of heterogeneous cDNA","volume":"87","author":"Yool","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gng015","article-title":"Summaries of Affymetrix GeneChip probe level data","volume":"31","author":"Irizarry","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1073\/pnas.091062498","article-title":"Significance analysis of microarrays applied to the ionizing radiation response","volume":"98","author":"Tusher","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1038\/s41423-021-00699-4","article-title":"Ribosomal protein S26 serves as a checkpoint of T-cell survival and homeostasis in a p53-dependent manner","volume":"18","author":"Chen","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.3892\/mmr.2016.5089","article-title":"Digital gene expression profiling analysis of childhood acute lymphoblastic leukemia","volume":"13","author":"Zhao","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9503","DOI":"10.2147\/IJGM.S343426","article-title":"Identification of a Lipid Metabolism-Associated Gene Signature Predicting Survival in Breast Cancer","volume":"14","author":"Gong","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s12276-020-00547-x","article-title":"Phospholipid dynamics in ex vivo lung cancer and normal lung explants","volume":"53","author":"Lesko","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"797","DOI":"10.3109\/10428194.2015.1088651","article-title":"A link between hypercholesterolemia and chronic lymphocytic leukemia","volume":"57","author":"Chow","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ebiom.2016.11.033","article-title":"Low Density Lipoproteins Amplify Cytokine-signaling in Chronic Lymphocytic Leukemia Cells","volume":"15","author":"McCaw","year":"2017","journal-title":"eBioMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.eururo.2017.08.027","article-title":"Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression","volume":"73","author":"Ren","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3892\/ol.2017.6183","article-title":"Screening of potentially crucial genes and regulatory factors involved in epithelial ovarian cancer using microarray analysis","volume":"14","author":"Shi","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jocn.2011.04.047","article-title":"Downregulation of PCDH9 predicts prognosis for patients with glioma","volume":"19","author":"Wang","year":"2012","journal-title":"J. Clin. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10287","DOI":"10.18632\/oncotarget.14396","article-title":"Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10585-015-9712-7","article-title":"Loss of PCDH9 is associated with the differentiation of tumor cells and metastasis and predicts poor survival in gastric cancer","volume":"32","author":"Chen","year":"2015","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Youn, M., Smith, S.M., Lee, A.G., Chae, H.D., Spiteri, E., Erdmann, J., Galperin, I., Jones, L.M., Donato, M., and Abidi, P. (2021). Comparison of the Transcriptomic Signatures in Pediatric and Adult CML. Cancers, 13.","DOI":"10.3390\/cancers13246263"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1007\/s00277-021-04615-8","article-title":"Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells","volume":"100","author":"Baumeister","year":"2021","journal-title":"Ann. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"881","DOI":"10.5114\/aoms.2016.60973","article-title":"Identification of differentially expressed genes in salivary adenoid cystic carcinoma cells associated with metastasis","volume":"12","author":"Chen","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Knott, E.L., and Leidenheimer, N.J. (2020). A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228485"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbrc.2017.08.114","article-title":"GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer","volume":"492","author":"Jin","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3892\/ol.2020.11573","article-title":"Distinct diagnostic and prognostic values of \u03b3-aminobutyric acid type A receptor family genes in patients with colon adenocarcinoma","volume":"20","author":"Yan","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"242","DOI":"10.21037\/atm.2020.01.12","article-title":"A predictive analysis approach for paediatric and adult high-grade glioma: miRNAs and network insight","volume":"8","author":"Liu","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Belotti, Y., Tolomeo, S., Yu, R., Lim, W.T., and Lim, C.T. (2022). Prognostic Neurotransmitter Receptors Genes Are Associated with Immune Response, Inflammation and Cancer Hallmarks in Brain Tumors. Cancers, 14.","DOI":"10.3390\/cancers14102544"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gross, A.M., Kreisberg, J.F., and Ideker, T. (2015). Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142618"},{"key":"ref_43","first-page":"5653739","article-title":"The Effect of Fasting on Human Metabolism and Psychological Health","volume":"2022","author":"Wang","year":"2022","journal-title":"Dis. Markers"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1111\/cas.15492","article-title":"Effect of fasting on cancer: A narrative review of scientific evidence","volume":"113","author":"Tiwari","year":"2022","journal-title":"Cancer Sci."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/8\/1405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:25Z","timestamp":1760127805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/8\/1405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["medicina59081405"],"URL":"https:\/\/doi.org\/10.3390\/medicina59081405","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]}}}