The lineage involvement in myelodysplastic syndromes (MDS) is still unclear. To determine the clonality and the evolution of the disorder, a retrospective study on bone marrow smears from seven MDS ...patients with trisomy 8 was performed using fluorescence
in situ hybridization (FISH).
We observed that the trisomy of chromosome 8 was selectively expressed in the myeloid-derived cells. No mature lymphocytes or plasma cells expressed three signals.
Our studies demonstrate here the value of FISH for identifying the affected cell lineage. Furthermore, the easy quantification of the abnormal cells can help in assessing the progression of the disease.
Preclinical studies and retrospective evaluations of clinical trials of a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid ...leukemia (AML). To maximize cure and remission rates at an acceptable cost in toxicity, many schedules and combinations of dose-intensive chemotherapy have been tested in recent years in patients with
de novo disease, cytosine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and non-controlled studies. Our analysis indicates that high-dose Ara-C (HIDAC) used during induction results is no substantial benefit relative to conventional doses of drug. On the other hand, consolidation with HIDAC is a major advance in the treatment of this disease. In fact, in individuals less than 60 years of age and a favorable or intermediate-risk karyotype, HIDAC-based regimens have resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Yet, the role of HIDAC is irrelevant in younger individuals with an unfavorable cytogenetic pattern and detrimental in patients greater than 60 years of age. Since recently new cytotoxic agents have expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy still need to be performed to optimize schedules and combinations of drugs in patients with AML.
Solitary loss of the X chromosome is associated with Turner syndrome and not hematological disorders. We describe five patients with non-constitutional loss of the X chromosome as the sole ...cytogenetic abnormality in their bone marrow. Three of the five patients had myelodysplastic syndrome (MDS), one case had AML M-6 with evidence suggestive of an evolving MDS, and the last patient had a dysplastic marrow. A review of the literature identified sporadic reports of an association of monosomy X and several hematologic disorders, as well as a few solid tumors. In this series of patients, monosomy X as a sole non-constitutional cytogenetic abnormality in bone marrow is associated with myelodysplastic diseases. In addition, fluorescence in situ hybridization analysis with an X centromere probe indicated that monosomy X was present in erythroid precursors, myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, and monocytes, while mature lymphocytes presented with two copies of the X chromosome. The molecular cytogenetic evidence supports the diagnosis of a myelodysplastic disorder in these cases and documents the potential role of FISH in hematological diseases.
Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy ...to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM. Our findings show that melphalan, a genotoxic agent used in MM therapy, significantly induces an increased exosome release from MM cells. MM cell-derived exosomes are capable of stimulating IFNγ production, but not the cytotoxic activity of NK cells through a mechanism based on the activation of NF-κB pathway in a TLR2/HSP70-dependent manner. Interestingly, HSP70
+
exosomes are primarily found in the bone marrow (BM) of MM patients suggesting that they might have a crucial immunomodulatory action in the tumor microenvironment. We also provide evidence that the CD56
high
NK cell subset is more responsive to exosome-induced IFNγ production mediated by TLR2 engagement. All together, these findings suggest a novel mechanism of synergism between chemotherapy and antitumor innate immune responses based on the drug-promotion of nanovesicles exposing DAMPs for innate receptors.
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