Disease relevance of ASZ1

• EspG, a secreted effector of enteropathogenic Escherichia coli (EPEC), as well as its homologue Orf3, has been shown to disrupt microtubules (MTs) in fibroblasts and non-polarized epithelial cells [1].
• Natural killer (NK) cell-type lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the outgrowth of CD3(-)CD16/56(+) NK cells, and can be further subdivided into two distinct categories: aggressive NK cell leukemia (ANKL) and chronic NK lymphocytosis (CNKL) [2].
• One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs [3].
• The morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non-T, non-B natural killer cell leukaemia/lymphoma (ANKL/L) are described [4].

High impact information on ASZ1

• Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL) [3].
• ANKL cells showed enhanced chemotaxis toward the ligands of these receptors [3].
• Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors [3].
• The Orf3 protein is also known to associate with and cause the reorganization of cell nucleus structures known as ND10 or PODs [5].
• Here we show that 55K also associates with Orf3 and that this interaction is necessary for 55K to localize to the nuclear matrix fraction of the cell [5].

Biological context of ASZ1

• In addition, these ANKL/L belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta, T gamma and T delta receptors, and immunoglobulin [4].
• After comparing them with the seven cases of ANKL/L reported in other institutions, with regard to immunophenotype, genotype and function, we conclude that ANKL/L originating from a third lineage of lymphoid cells is a distinct clinical entity [4].

Analytical, diagnostic and therapeutic context of ASZ1

• Systemic chemotherapy resulted in complete remission in one ANKL/L and two blastic NK cell leukaemia/lymphoma (BNKL/L) patients; however, a good long-term outcome was achieved in only one CD4-positive BNKL/L patient with allogenic bone marrow transplantation [6].

References