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

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.

Factors influencing [F-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) uptake in melanoma cells: the role of proliferation rate, viability, glucose transporter expression and hexokinase activity.

Using human (SK-MEL 23, SK-MEL 24 and G361) and murine (B16) melanoma cell lines, the coregulatory potential of the uptake of the positron emission tomography (PET) tracer, [Fluorine-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) has been investigated in relationship to tumor characteristics. Comparative studies among the four melanoma cell lines demonstrated that the lowest FDG uptake in SK-MEL 24 corresponded strongly to the data for DT (population doubling time) and MTT (tetrazolium salt) cell viability as well as hexokinase (HK) activity, but was not related to the glucose transporter 1 (GLUT 1) expression level. Furthermore, the FDG uptake in each melanoma cell line measured by cell cycle kinetics was significantly positively correlated to both the proliferation index (PI=S/G2M phase fractions) and the cell viability, though with one exception relating to the PI of the lowest FDG uptake cell line, SK-MEL 24. No positive correlation was found between the expression of GLUT 1 and FDG uptake in any individual cell line. However, the HK activities in SK-MEL 23 and 24 showed considerable positive relationships with FDG uptake. Our present study suggests that both the proliferation rate and the cell viability of melanoma cells may be key factors for FDG uptake and that HK activity, rather than GLUT 1 expression, seems to be a major factor.

Factors influencing [F-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) accumulation in melanoma cells: is FDG a substrate of multidrug resistance (MDR)?

In order to specify the influence of multidrug-resistance (MDR) on the accumulation of the PET tracer, F-18 FDG ([Fluorine-18] 2-fluoro-2-deoxy-D-glucose, in melanoma cells, both the MDR function and expression of two human melanoma cell lines SK-MEL 23 and 24, were evaluated. The effects of MDR modulators on FDG accumulation and efflux were also investigated. A functional analysis using representative MDR fluorescent substrates and inhibitors clarified the following characteristics: 1) SK-MEL 23 possesses a highly active function of MRP, but not P-gp. 2) SK-MEL 24 possesses weak functions of both MRP and P-gp. Western blot analysis using monoclonal antibodies for MDR expression demonstrated an exceedingly high MRP expression of SK-MEL 23 and only slight P-gp and MRP expression of SK-MEL 24, corresponding to the functional data. The efflux inhibition assay using F-18 FDG revealed a considerable retention of FDG in SK-MEL 23 in the presence of the MRP inhibitor probenecid. It was also found that the P-gp inhibitor verapamil depressed the FDG efflux of SK-MEL 24. Our present in vitro study suggests that FDG may be a substrate of MDR in some melanoma cells and further MDR may be one of the important factors affecting FDG-PET melanoma imaging.

Hematologic and molecular spontaneous remission following sepsis in acute monoblastic leukemia with translocation (9;11): a case report and review of the literature.

Spontaneous remission in patients with acute myeloid leukemia (AML) is a rarely reported phenomenon of usually short duration. The etiology remains unclear, but an association with preceding blood transfusions or bacterial infections has been reported. Triggered immune responses are suggested to play a potential role in the development of spontaneous remission. Acute monocytic leukemia was diagnosed in a 61-yr-old male patient. Cytogenetic analysis revealed a sole translocation (9;11) (q22;q23) and RT-PCR the MLL/AF9 fusion gene. As a result of the patient's reduced performance status and septic condition, cytostatic therapy was withheld. No microorganisms could be detected. Hematologic and molecular remission occurred after initiating antibiotic therapy without any cytostatic treatment; 29 months after the initial diagnosis, he is in complete remission, and excellent physical condition. Our report includes a review of the literature since 1985, reporting cases of patients with AML and spontaneous remission together with informative cytogenetics. Balanced translocations such as in core binding factor (CBF) leukemias appear somewhat overrepresented. We speculate that AML-specific T cells might be relevant for induction of spontaneous remission and need to be further investigated.

Myelodysplastic syndrome in transformation to acute myeloid leukemia presenting with diabetes insipidus: due to pituitary infiltration association with abnormalities of chromosomes 3 and 7.

A 31-yr-old woman with myelodysplastic syndrome (MDS) in transformation to acute myeloid leukemia (AML) presented with initial symptoms of polyuria and polydipsia. Cytogenetics revealed monosomy 7 and translocation (3;3)(q21;q26). The initial symptoms, in conjunction with a low serum level of anti-diuretic hormone (ADH) and magnetic resonance imaging (MRI) findings demonstrating loss of the "bright spot" of the neurohypophysis, indicated diabetes insipidus (DI), e.g. caused by leukemic infiltration of the neurohypophysis. After induction chemotherapy the patient's bone marrow revealed blast persistence, and following a second course of chemotherapy and normalisation of MRI, an allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-identical brother was performed, resulting in ongoing complete remission. Recently, Lavabre-Bertrand et al. reported an association of AML with DI, elevated platelet counts, and monosomy 7 and chromosome 3 abnormalities in three patients (Eur. J. Haematol. 2001: 66: 66-69). Our report of an MDS with trilineage dysplasia and these karyotypic changes associated with DI indicates that this new entity may also include preleukemic cases.