{"doi":"10.1172/jci143119","title":"Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia","abstract":"PFKP (phosphofructokinase, platelet), the major isoform of PFK1 expressed in T cell acute lymphoblastic leukemia (T-ALL), is predominantly expressed in the cytoplasm to carry out its glycolytic function. Our study showed that PFKP is a nucleocytoplasmic shuttling protein with functional nuclear export and nuclear localization sequences (NLSs). Cyclin D3/CDK6 facilitated PFKP nuclear translocation by dimerization and by exposing the NLS of PFKP to induce the interaction between PFKP and importin 9. Nuclear PFKP stimulated the expression of C-X-C chemokine receptor type 4 (CXCR4), a chemokine receptor regulating leukemia homing/infiltration, to promote T-ALL cell invasion, which depended on the activity of c-Myc. In vivo experiments showed that nuclear PFKP promoted leukemia homing/infiltration into the bone marrow, spleen, and liver, which could be blocked with CXCR4 antagonists. Immunohistochemical staining of tissues from a clinically well-annotated cohort of T cell lymphoma/leukemia patients showed nuclear PFKP localization in invasive cancers, but not in nonmalignant T lymph node or reactive hyperplasia. The presence of nuclear PFKP in these specimens correlated with poor survival in patients with T cell malignancy, suggesting the potential utility of nuclear PFKP as a diagnostic marker.","journal":"Journal of Clinical Investigation","year":2021,"id":157687,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":665024,"name":"Shenghui Qin","orcid":"0000-0003-0363-7675","position":1,"is_corresponding":false},{"id":443740,"name":"Yongxia Wu","orcid":"0000-0003-1568-2377","position":2,"is_corresponding":false},{"id":269983,"name":"Chen Chu","orcid":"0000-0001-8084-0867","position":3,"is_corresponding":false},{"id":347440,"name":"Baishan Jiang","orcid":"0000-0001-6796-9500","position":4,"is_corresponding":false},{"id":665659,"name":"Roger H. Johnson","orcid":null,"position":5,"is_corresponding":false},{"id":244656,"name":"Dong Kuang","orcid":"0000-0002-8455-3379","position":6,"is_corresponding":false},{"id":426397,"name":"Jie Zhang","orcid":"0000-0002-0466-2955","position":7,"is_corresponding":false},{"id":665025,"name":"Xi Wang","orcid":"0000-0001-8517-9828","position":8,"is_corresponding":false},{"id":262766,"name":"Anand S. Mehta","orcid":"0000-0002-9846-9389","position":9,"is_corresponding":false},{"id":104376,"name":"Kenneth D. Tew","orcid":"0000-0002-2117-7521","position":10,"is_corresponding":false},{"id":316405,"name":"Gustavo Leone","orcid":"0000-0002-7617-7449","position":11,"is_corresponding":false},{"id":321624,"name":"Xue‐Zhong Yu","orcid":"0000-0002-1751-2884","position":12,"is_corresponding":false},{"id":665026,"name":"Haizhen Wang","orcid":"0000-0003-3477-8673","position":13,"is_corresponding":false},{"id":665023,"name":"Xueliang Gao","orcid":"0000-0003-4834-0437","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:44:21.786014Z","pmid":"34255748","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}