Combined CXCR3/CXCR4 measurements are of high prognostic value in chronic lymphocytic leukemia due to negative co-operativity of the receptors

High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones

“…Recently, CXCR3 has been found as a marker of independent prognostic significance in CLL [ 26 ]. High CXCR3 expression and CXCR3/CXCR4 ratio delineated patients with a significantly better clinical course, as opposed to patients with low CXCR3 and high CXCR4 expression [ 26 , 27 ]. To date, there is no clear understanding of how CXCR3 influences the pathogenesis of CLL.…”

“…To date, there is no clear understanding of how CXCR3 influences the pathogenesis of CLL. A formation of CXCR3-CXCR4 heteromers and a negative binding cooperativity between CXCR3 and CXCR4 at the cell surface was reported on CLL [ 26 ] and HEK293T [ 28 ] cells. Importantly, the CXCR3-CXCR4 heteromerization has been shown to alter the ligand-binding kinetics: CXCR3 and CXCR4 agonists have been proved to inhibit each other's equilibrium binding on membranes and specifically accelerate dissociation of CXCL12 from CXCR4 [ 28 ].…”

BCR and chemokine responses upon anti-IgM and anti-IgD stimulation in chronic lymphocytic leukaemia

“…Furthermore, CXCR3 is expressed on CLL in variable amounts, in contrast to other B cell lymphomas. High CXCR3 expression levels are associated with indolent disease, exerting a negative functional regulation on CXCR4 [25]. In healthy B cells, activation of the BCR fundamentally alters the expression and function of CXCR4 [26], CCR7, and CXCR5 [27].…”

MRI and PET/MRI in hematologic malignancies

“…Whether the combination of DWI with [ 68 Ga]Ga‐Pentixafor is clinically useful in the sense of providing a multimodal oncologic "signature" for leukemias is yet to be determined. The two main arguments for the use of [ 68 Ga]Ga‐Pentixafor‐PET in CLL are that high CXCR4 expression is known to be associated with poor prognosis in CLL, and that—similar to myeloma—[ 68 Ga]Ga‐Pentixafor‐PET might enable the selection of patients for systemic treatment with [ 177 Lu]Pentixather. In this setting, ADCs might serve as a surrogate marker for treatment response whose biologic correlate—ie, cell density—is at least partly independent of CXCR4 expression.…”