Deficient expression of class-I HLA in some cases of acute leukemia

Abstract

Leukemic cells from the blood and marrow of 25 cases of newly diagnosed acute leukemia were presented as target cells to alloreactive effector cells from unrelated normal donors in cell-mediated cytotoxicity assays. In three cases the leukemic targets were poorly killed relative to nonleukemic, HLA-identical target cells. The poor killing of the leukemic cells from one of these cases was shown by competitive inhibition to be due to deficient expression of normal class-I HLA antigens rather than resistance to lysis. Furthermore, the leukemic cells from these three patients were also deficient in binding monoclonal antibodies to nonpolymorphic determinants of class-I HLA and B2 microglobulin. Two additional cases were identified as having a less extensive deficit of HLA, and may be representative of a group with relatively subtle changes in these cell surface antigens. The possible significance of reduced expression of HLA in leukemic progression and in susceptibility to graft-vs-leukemia reactions after bone marrow transplantation is discussed.

Identification of natural killer cell receptor phenotypes associated with leukemia

“…It has been reported that leukemic cells can have downregulated expression of HLA class I molecules and in some situations show a complete loss of a HLA class I allele. [17][18][19][20] Apparently, the NK cells of these patients are not able to destroy …”

“…14, 15 The CD94/ NKG2 heterodimers has been shown to recognize the nonclassical HLA-E molecule and depending on the type of NKG2 receptor the generated signal can be inhibiting (NKG2A) or activating (NKG2C and NKG2E). 16 Recently, our 17 and other studies [18][19][20] demonstrated that leukemic cells can have downregulated expression of HLA class I molecule and putative allele loss. [17][18][19][20] Moreover, recent studies support a major role for NK cells in the graft-versusleukemia effect in allogeneic stem cell transplantation.…”

“…16 Recently, our 17 and other studies [18][19][20] demonstrated that leukemic cells can have downregulated expression of HLA class I molecule and putative allele loss. [17][18][19][20] Moreover, recent studies support a major role for NK cells in the graft-versusleukemia effect in allogeneic stem cell transplantation. [21][22][23] These data demonstrate that NK cells could play an important role in the innate immune surveillance of leukemic cells.…”

New approaches in the immunotherapy of haematological malignancies

“…Deficient HLA class I expression has been described in leukaemia (23). This abnormal class I molecule expression may favour escape from conventional Cytotoxic T-Lymphocytes (CTLs) ( Fig.…”

Receptor Activator for NF-κB Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance

“…Their involvement in immunosurveillance of hematopoietic malignancies and in particular acute myeloid leukemia (AML) is highlighted by studies on haploidentical stem cell transplantation \(SCT), where the recipient's leukemia cells fail to inhibit donor NK cells via killer Ig-like receptors (KIRs), and KIR disparity is associated with powerful graft versus leukemia effects and better clinical outcome (2)(3)(4). The observation that leukemia cells may downregulate HLA class I molecules (5,6), presumably to escape adaptive immunity, suggests that NK cells are also involved in controlling leukemia in an autologous setting. This is also supported by the observation that NK cell counts and activity are reduced in patients with leukemia and that activity levels of autologous NK cells are associated with survival of leukemia patients (7)(8)(9).…”