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Diagnosis of myelodysplastic syndromes (MDS) is not straightforward when objective data, such as blast excess and abnormal cytogenetics, are lacking. Expert laboratories use flow cytometry (FCM) to help diagnose MDS. However, most of FCM protocols for MDS are complex, requiring a high level of expertise and high cost. We have reported a FCM mini-panel consisting of four FCM parameters (so-called Ogata score), which is simple to conduct and inexpensive. In this paper, to refine this mini-panel, we have introduced a new FCM parameter, which quantifies CD33 expression on CD34+ cells (called Granulocyte/CD34 cell CD33 ratio). Bone marrow cells from MDS without blast excess (low-grade MDS) and controls were stained with CD34, CD45, and CD33 and analyzed for five parameters ("Granulocyte/CD34 cell CD33 ratio" plus four parameters in the Ogata score). By a multivariate logistic regression model, only three parameters, including "Granulocyte/CD34 cell CD33 ratio" had statistically significant power for diagnosing low-grade MDS. Based on the results, we constructed a new scoring system, which showed approximately 50% sensitivity and more than 95% specificity in diagnosing low-grade MDS. Our revised mini-panel is suitable for screening samples suspected for MDS and provides a basis for further improvement in diagnostic FCM protocols for MDS., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Myelodysplastic syndromes (MDS) often transform into acute leukemia (AL-MDS), although its prognostic details have not been examined thoroughly. We retrospectively analyzed the prognosis of 189 AL-MDS patients. Ninety-four patients received best supportive care (BSC), and 94 patients received disease-modifying therapies (DMT) that included chemotherapy (CHT) for 65 patients, allogeneic stem-cell transplantation (allo-SCT) for 21 patients, and other therapies for 8 patients. The median survival time was 142 days. In patients treated with BSC, platelet count alone was an independent prognostic factor. In younger patients treated with DMT (<60 years, N=25), allo-SCT was an independent prognostic factor associated with longer survival. In older patients treated with DMT (≥60 years, N=69), the therapy type did not affect survival, and performance status and MDS-specific comorbidity index were independent prognostic factors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We conducted a multicenter, flow cytometry study to validate differences in immunophenotypes among disease types in melodysplastic syndromes (MDS). The data obtained from 115 patients were combined into three groups according to disease grade, i.e., low-grade MDS, refractory anemia with excess blasts, and acute leukemia transformed from MDS (AL-MDS). The data comparison showed that with the progression of disease grade, the immunophenotypes of CD34(+) myeloblasts were more immature, with an increase and a decrease in CD7 and CD15 expression, respectively, and the percentages of CD34(+) B-progenitors among total CD34(+) cells and the granularity of granulocytes decreased. Logistic regression analyses showed that, in addition to myeloblast percentages, the expression of CD7 and B7-H1 on myeloblasts was independently associated with AL-MDS patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The somatic mutation theory proposing that a sequential accumulation of genetic abnormalities plays a major role in cancer pathogenesis has not yet been confirmed for myelodysplastic syndromes (MDS). Meanwhile, recent data in some cancers has underscored the role of the microenvironment in tumor growth. MDS CD34+CD38- cells usually fail to repopulate after transplantation in mice, suggesting the importance of the microenvironment for MDS cells. Our recent data have provided a disease-progression model in which overproduction of interferon-γ and tumor necrosis factor-α in the microenvironment is the primary event. This causes B7-H1 molecule expression on MDS blasts, which generates a bifunctional signal inducing T-cell apoptosis and enhancing blast proliferation. The latter may provide more opportunity for developing secondary genetic changes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Wilms tumor gene (WT1) mRNA expression in peripheral blood cells was examined in 80 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) transformed from MDS. Serum anti-WT1 antibody titers were also determined in 45 patients. Their long-term follow-up showed that the survival rate became worse as the WT1 mRNA level increased. In particular, a high WT1 mRNA level was a strong predictor of a short time to AML transformation even if adjusted by the International Prognostic Scoring System category. Moreover, high values of anti-WT1 antibody were an independent predictor of longer survival. These data may justify therapeutic strategies targeting WT1 molecules in MDS., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Clinical data suggest that CD7+ myeloblasts are linked with poor prognosis in myeloid malignancies including myelodysplastic syndromes (MDS). To explore the biology behind this, we compared cell characteristics between CD34+CD7+ and CD34+CD7- myeloblasts from an MDS cell line and fresh samples from MDS patients. Compared with CD34+CD7- myeloblasts, CD34+CD7+ myeloblasts showed greater proliferative capacity, more active cell cycling, and less apoptosis. In analyses of a cell line, CD34+CD7+ myeloblasts produced CD34+CD7- myeloblasts and showed lower expressions of interleukin-8 and chemokine (C-C motif) ligand 2 genes, suggesting immaturity of these cells. These findings might underlie the clinical aggressiveness in CD7+ MDS.

Recent studies have suggested that flow cytometry (FCM) helps diagnose myelodysplastic syndromes (MDS). However, appropriate FCM diagnostic parameters that are easily reproducible by different examiners remain unclarified. We found that "the Ly/Mbl CD45 ratio (mean fluorescence intensity [MFI] of CD45 on lymphocytes/MFI of CD45 on CD34+ myeloblasts)," "the percentage of CD34+ myeloblasts among all nucleated cells," and "the percentage of CD34+ B-cell precursors among all CD34+ cells" had little interexaminer variability. These parameters can be analyzed from one test tube for three-color FCM, and their analysis in combination can diagnose a certain percentage of low-grade MDS patients.

The mechanism of T cell lymphopenia in myelodysplastic syndromes (MDS) is unknown. We investigated apoptosis in freshly isolated and cultured lymphocytes; the latter were used to detect cells not yet apoptotic but destined for apoptosis. Apoptosis increased in both fresh and cultured T cells in MDS compared with those from healthy controls. Furthermore, in lymphopenic MDS patients the lymphocyte count correlated negatively with the degree of T cell apoptosis. MDS T cells showed increased Fas expression. However, in MDS but not in controls, the degree of T cell apoptosis was independent of the Fas expression level, and exogenous anti-Fas antibodies did not modulate T cell apoptosis. Mechanisms other than the Fas-Fas ligand pathway may induce T cell apoptosis in MDS.

The classification, scoring systems, and response criteria for myelodysplastic syndromes (MDS) have recently been updated and have become widely accepted. In addition, several new effective targeted drugs for patients with MDS have been developed. The current article provides a summary of updated and newly proposed markers, criteria, and standards in MDS, with special reference to the diagnostic interface and refinements in evaluations and scoring. Concerning the diagnostic interface, minimal diagnostic criteria for MDS are proposed, and for patients with unexplained cytopenia who do not fulfill these criteria, the term 'idiopathic cytopenia of uncertain significance' (ICUS) is suggested. In addition, new diagnostic and prognostic parameters, histopathologic and immunologic determinants, proposed refinements in scoring systems, and new therapeutic approaches are discussed. Respective algorithms and recommendations should facilitate diagnostic and prognostic evaluations in MDS, selection of patients for therapies, and the conduct of clinical trials.

The transformation site in acute myeloid leukemia (AML) has been proposed to be pluripotent hematopoietic stem cells (PHSCs), and the lymphoid development of leukemic PHSCs may be suppressed by leukemogenic events. Recent data from multiple laboratories have contradicted the current hierarchical model of hematopoiesis and indicated the presence of myeloid HSCs with minimal lymphopoietic potential (MyHSCs) in mice. Based on these findings and re-evaluating the published data on AML stem cells, we hypothesize that MyHSCs may be the transformation site in AML. If so, therapy targeting leukemic MyHSCs but sparing PHSCs is worth investigating.

Although the blast percentage in the bone marrow (BM) is a key parameter for the classification of myelodysplastic syndromes (MDS), the current blast percentages used to define MDS subtypes have not been shown to have strong biological relevance. We determined the blast phenotypes and examined their relationship with the BM blast percentage in 90 MDS cases. When the BM blast percentage increased, cases whose blasts expressed CD7, CD56 and CD117 increased whereas cases whose blasts expressed CD10, CD11b and CD15 decreased. The BM blast percentages where the blast immunophenotype changed were 5, 10, 20 and 25%. Blast immunophenotypes have the potential to provide a biological basis for and refine the present MDS classifications.