Serum Flt3 ligand is biomarker of progenitor cell mass and prognosis in acute myeloid leukemia
Serum Flt3 ligand is biomarker of progenitor cell mass and prognosis in acute myeloid leukemia
Abstract Fms-like tyrosine kinase 3 (Flt3) is a hematopoietic growth factor receptor expressed on lymphomyeloid progenitors and frequently, by AML blasts. Its ligand, Flt3L, has non-hematopoietic and lymphoid origins, is detectable during homeostasis and increases to high levels in states of hypoplasia due to genetic defects or treatment with cytoreductive agents. Measurement of Flt3L by ELISA reveals that Flt3+AML, is associated with depletion of Flt3L to undetectable levels. After induction chemotherapy, Flt3L is restored in patients entering CR, but remains depressed in those with refractory disease. Weekly sampling reveals marked differences in the kinetics of Flt3L response during the first 6 weeks of treatment, proportionate to the clearance of blasts and cellularity of the BM. In the UK NCRI AML17 trial, Flt3L was measured at day 26 in a subgroup of 135 patients with Flt3 mutation randomized to the tyrosine kinase inhibitor lestaurtinib. In these patients, attainment of CR was associated with higher Flt3L at day 26 (Mann-Whitney p < 0.0001). Day 26 Flt3L was also associated with survival: Flt3L ≤ 291pg/ml was associated with inferior event-free survival; and, Flt3L >1185pg/ml was associated with higher overall survival (p = 0.0119). Serial measurement of Flt3L in patients who had received a hematopoietic stem cell transplant for AML further illustrated the potential value of declining Flt3L to identify relapse. Together these observations suggest that measurement of Flt3L provides a non-invasive estimate of progenitor cell mass in most patients with AML, with the potential to inform clinical decisions. Graphical abstractbiorxiv;588319v1/UFIG1F1ufig1
Levis Mark、Burnett Alan、Russell Nigel、Grunwald Michael R.、Bigley Venetia、Publicover Amy、Pagan Sarah、Marr Helen、Jones Gail、Grech Angela、Knapper Steven、Milne Paul、Wilhelm-Benartzi Charlotte、Dickinson Anne、Collin Matthew
Division of Hematological Malignancies, Johns Hopkins Sidney Kimmel Cancer CenterDepartment of Haematology, Cardiff University School of MedicineDepartment of Haematology, Nottingham University HospitalDepartment of Hematologic Oncology and Blood Disorders, Levine Cancer InstituteInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK and NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne HospitalsNorthern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation TrustInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK and NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne HospitalsNorthern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation TrustNorthern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation TrustDepartment of Haematology, Cardiff University School of MedicineDepartment of Haematology, Cardiff University School of MedicineInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK and NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne HospitalsCentre for Trials Research, College of Biomedical and Life Sciences, Cardiff UniversityInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK and NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne HospitalsInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK and NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals
肿瘤学基础医学临床医学
Levis Mark,Burnett Alan,Russell Nigel,Grunwald Michael R.,Bigley Venetia,Publicover Amy,Pagan Sarah,Marr Helen,Jones Gail,Grech Angela,Knapper Steven,Milne Paul,Wilhelm-Benartzi Charlotte,Dickinson Anne,Collin Matthew.Serum Flt3 ligand is biomarker of progenitor cell mass and prognosis in acute myeloid leukemia[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/588319.点此复制
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