Background: Stable flow cytometric markers for malignant myeloid cells are highly warranted. Based on data from stem cell research, we hypothesized that the human inhibitory C-type lectin like receptor (hMICL) might represent a novel diagnostic and prognostic vehicle in a standard flow cytometry (FCM) setting.Methods: Standard four-color FCM was employed to uncover the expression patterns of hMICL in bone marrow in a test set of 55 retrospectively collected diagnostic acute myeloid leukemia (AML) samples and in a set of 36 prospectively collected diagnostic AML samples.Results: Ninety-two percent of the AML patients stained positive for hMICL and in the otherwise poorly characterized CD34 negative patient group hMICL staining revealed a very homogenous expression profile in the blast cell compartment with a mean of 88% hMICL positive cells. Moreover, hMICL displayed significantly higher expression in AML as compared with normal donors as measured by median fluorescence intensity (MFI) ratios (P 5 0.01). There was no difference in hMICL MFI ratios between the CD34 positive and the CD34 negative subgroups (P 5 0.89). Importantly, there was no difference in MFI ratios between paired diagnostic and relapse samples (P 5 0.76) in 23 cases studied, indicating stable expression of hMICL during the course of the disease. In contrast to the other stem cell associated antigens analyzed (CD34, CD96, CD117, and CD133), hMICL was expressed on myeloid blast cells only, revealing hMICL as a diagnostic marker in AML.Conclusion: These data identify hMICL as a myeloid leukemia-associated antigen and establishes its applicability for diagnosis and follow-up of AML patients in a standard FCM setting. V C 2011 International
MicroRNAs have the potential to be useful biomarkers in the development of individualized treatment since they are easy to detect, are relatively stable during sample handling, and are important determinants of cellular processes controlling pathogenesis, progression, and response to treatment of several types of cancers including B-cell malignancies. miR-155 is an oncomiR with a crucial role in tumor initiation and development of several B-cell malignancies. The present review elucidates the potential of miR-155 as a diagnostic, prognostic, or predictive biomarker in B-cell malignancies using a systematic search strategy to identify relevant literature. miR-155 was upregulated in several malignancies compared to nonmalignant controls and overexpression of miR-155 was further associated with poor prognosis. Elevated expression of miR-155 shows potential as a diagnostic and prognostic biomarker in diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Additionally, in vitro and in vivo studies suggest miR-155 as an efficient therapeutic target, supporting its oncogenic function. The use of inhibiting anti-miR structures indicates promising potential as novel anticancer therapeutics. Reports from 53 studies prove that miR-155 has the potential to be a molecular tool in personalized medicine.
SummaryReal-time quantitative polymerase chain reaction (qPCR) has been extensively validated for the detection of minimal residual disease (MRD) in acute myeloid leukaemia (AML). Meanwhile, multicolour flow cytometry (MFC) has received less attention because the so-called leukaemia-associated immunophenotypes (LAIPs) are generally of lower sensitivity and specificity, and prone to change during therapy. To improve MRD assessment by MFC, we here evaluate the combination of human Myeloid Inhibitory C-type Lectin (hMICL, also termed C-type lectin domain family 12, member A, CLEC12A) and CD 123 (also termed interleukin-3 receptor alpha, IL3RA) in combination with CD34 and CD117 (KIT), as an MRD assay in pre-clinical and clinical testing in 69 AML patients. Spiking experiments revealed that the assay could detect MRD down to 10 À4 in normal bone marrow with sensitivities equalling those of validated qPCR assays. Moreover, it provided at least one MFC MRD marker in 62/69 patients (90%). High levels of hMICL/ CD123 LAIPs at the post-induction time-point were a strong prognostic marker for relapse in patients in haematological complete remission (P < 0Á001). Finally, in post induction samples, hMICL/CD123 LAIPs were strongly correlated (r = 0Á676, P = 0Á0008) to applied qPCR targets. We conclude the hMICL/CD123-based MFC assay is a promising MRD tool in AML.
The C-type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia-associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking.Here, we have characterized the expression pattern of CLEC12A on the earliest stem-and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on to favour non-erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC12A + cell in the haematopoietic tree is the classically defined CMP.Furthermore, we show that CLEC12A-expressing CMPs and MEPs are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC12A-targeted therapy, and we propose CLEC12A to be included in future studies of myeloid cancer stem cell biology.
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