Immune response as a possible mechanism of long-lasting disease control in spontaneous remission of MLL/AF9-positive acute myeloid leukemia

Abstract

Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure). We could demonstrate strong in vitro cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis 2001) against myeloid cell lines. We also addressed cellular cytotoxic activity against myeloid leukemia cells. When the patient's natural killer (NK) cells (obtained in 2007) were tested against the K562 cell line, upregulation of CD107 occurred, implying that long-term CR in this patient could be due to NK cell-mediated disease control.

Spontaneous Remission in an Older Patient with RelapsedFLT3ITD Mutant AML

“…Hypergammaglobulinemia, representing humoral immune response, can occur secondary to antibody generation against blast antigens, antibody generation triggered by cytotoxic T-cell lymphocyte recognition of blasts, or antibody generation against infectious antigens with cross-reactivity to leukemic blasts [4, 36]. This may also contribute to increased antibody-mediated cytotoxicity via NK and cytotoxic T-cells and activate macrophages through better recognition, opsonization, or adhesion [37, 38]. In vitro experiments performed at 10-year follow-up of the longest sustained SR in AML containing the t (9; 11)(q22; q23) abnormality suggested that early immune effects were likely mediated by CD8 T-cell and humoral mechanisms while long-term remission was potentially mediated by NK-cells [38, 39].…”

“…This may also contribute to increased antibody-mediated cytotoxicity via NK and cytotoxic T-cells and activate macrophages through better recognition, opsonization, or adhesion [37, 38]. In vitro experiments performed at 10-year follow-up of the longest sustained SR in AML containing the t (9; 11)(q22; q23) abnormality suggested that early immune effects were likely mediated by CD8 T-cell and humoral mechanisms while long-term remission was potentially mediated by NK-cells [38, 39]. …”

Lorenz system in the thermodynamic modelling of leukaemia malignancy

“…The underlying molecular mechanisms of spontaneous remission are still unknown. The activation of cytotoxic T lymphocytes and macrophages, in conjunction with an increased cytotoxicity of natural killer cells [38] as well as cytokines of the immune system, such as tumour necrosis factor [39,40], interferon gamma and interleukin-2, released during infection, may play a role in the occurrence of spontaneous remission [41,42]. However, no clear link between spontaneous remission and infection or immune response was reported in at least one case [43].…”

Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction

“…Recently, targeted molecular therapies and immunebased therapies, such as the leukemia-associated antigen vaccine and antigen-specific cytotoxic T cells, are under investigation for the management of high-risk AML (Greiner et al, 2008;Sasine and Schiller, 2015). Long-term complete remission was demonstrated for some AML cases with cellular cytotoxic activity against myeloid leukemia cells (Müller-Schmah et al, 2012).…”

“…T cell immunodeficiency plays an important role in cancer and leukemia progression and promotes the expansion of malignant clones (Greiner et al, 2008;Müller-Schmah et al, 2012). Recent studies have revealed that T cell immunodeficiencies are common characteristics of patients with AML, and they are characterized by peripheral T cells that are incapable of interacting with blasts, reduced thymic output function, oligoclonally restricted T cell repertoires, and low activation and response to antigens.…”