We show here for the first time that LPXN is a fusion partner of ETV6 and present evidence indicating that ETV6-LPXN plays a crucial role in leukemia progression through enhancing the response to G-CSF and CXCL12.
These findings raised the questions how CSF3R mutations affect CSF3 responses of myeloid progenitors, how they contribute to the pre-leukemic state of SCN, and which additional events are responsible for progression to leukemia.
Hematopoietic stem cell transplantation remains the only currently available treatment for refractory cases to G-CSF and patients who have transformed into leukemia.
We evaluated the safety and efficacy of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor priming and short-term immunosuppressive agents for prophylaxis of relapse in patients with advanced leukemia after human leukocyte antigen (HLA)-mismatched T cell-replete hematopoietic stem cell transplantation (HCT).
One possible pathomechanism causing leukemia is that clones of cells harboring acquired CSF3R mutations have a growth advantage over wild type cells in vivo during granulocyte-colony stimulating factor treatment due to activation of STAT5 and ss-catenin, both known to be involved in leukemogenesis.
Point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R have been implicated in the progression of severe congenital neutropenia (CN) to leukemia.
Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.
In addition to the ability of G-CSF to stimulate the maturation and function of granulocytes, experimental and clinical evidence suggests that induction of leukemia cell differentiation may also be possible.
Optimization of gene transfer into primitive human hematopoietic cells of granulocyte-colony stimulating factor-mobilized peripheral blood using low-dose cytokines and comparison of a gibbon ape leukemia virus versus an RD114-pseudotyped retroviral vector.
We compared transduction of autologous B-cell lines and granulocyte colony-stimulating factor-mobilized peripheral CD34(+) cells from these patients using an MFGS retrovirus vector containing the gamma(c) gene IL2RG pseudotyped with amphotropic, gibbon ape leukemia virus, or RD114 envelopes.
The presence of G-CSF receptors was demonstrated in 4/14 (29%) patients, two with ALL, one with CLL, and one with CML-LBC, and was associated with stimulation of leukemia clonogenic cell growth by G-CSF.
We studied nine patients affected by chronic myeloid leukemia (CML Ph+ and bcr-abl positive) and treated with alpha-interferon (alpha-INF) in order to: first, to evaluate the feasibility of a mobilization of peripheral blood stem cells induced by granulocyte-colony-stimulating factor (G-CSF) and the contamination by Ph+ cells and second, to quantify the amount of bcr-abl leukemia associated transcript by a quantitative assay during mobilization procedures, and post mobilization follow-up.
Nevertheless, DAB486-G-CSF may be included with the increasing number of other toxin-hormone fusion proteins whose toxicity is directed towards specific receptor-bearing cells, and may represent a novel approach towards the study and treatment of leukemia.
This property of G-CSF has led to suggestions that its absence is responsible for lack of differentiation of leukemic cells and that the therapeutic administration of G-CSF could reverse this defect and result in a cure for leukemia.