In Chronic Myeloid Leukemia (CML) patients, CD34+/CD38-/CD26+ cell population represents a “CML specific” Leukemia Stem Cell (LSC) compartment. Indeed, preliminary studies showed that the expression of CD26 discriminates bone marrow CML Leukemic Stem Cells (LSCs) from nor-mal Hematopoietic Stem Cells (HSCs) or from LSCs of other myeloid neoplasms. We were first to demonstrate that at diagnosis CD34+/CD38-/CD26+ cells are easily measurable also in Peripheral Blood (PB) and that residual circulating CD26+LSCs persist, with a fluctuating trend, in most pa-tients in optimal response during treatment with Tyrosine Kinase Inhibitors (TKIs) and even after successful TKI discontinuation. These data corroborate and confirm the possibility of using flow-cytometry CD26+ evaluation as an important diagnostic tool that, combined with molecular biology and cytogenetic, could provide a rapid diagnosis of Chronic Phase (CP) CML starting from a simple PB sample. Yet, few data are available regarding the behavior of CD26+LSCs during Accelerated Phase (AP) or Blast Phase (BP) CML and the role, if any, this peculiar staminal cell compartment may play in disease progression. In the present study we compared the presence and phenotypic characteristics of circulating CD26+LSCs in CP CML patients at diagnosis, during AP and in cases of progression to lymphoid BP, inquiring a possible role of these cells during dis-ease evolution.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, AML have not yet identified effective treatments or expanded diagnostic or prognostic markers. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSC) consist of hematopoietic stem cells (HSC) and cancer cells transformed by the complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSC dormancy, its diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML were discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSC, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveals that microRNAs are a unique factor for LSC. Furthermore, multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSC, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predicted that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes enabled achievable by Network Pharmacology research.

ALDH+ H1975 lung adenocarcinoma stem cells (LSCs) are a rare cell population identified in lung adenocarcinoma (LUAD). LSCs can self-renew, drive tumor initiation, growth, metastasis, and recurrence, and are also the predominant cause of poor prognosis due to their intrinsic resistance to drugs and chemotherapy. Consequently, LSCs are a promising target for LUAD therapy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), exert many significant regulatory functions in the pathogenesis of human cancers, showing the necessity for a comprehensive understanding of the mechanisms that underlie lung carcinogenesis. Nonetheless, research on many known transcripts and messenger RNAs (mRNAs) has already generated new information. Unknown biomarkers in ncRNAs and systematic and comprehensive interrelation with unknown ncRNAs and mRNAs may provide further insights into the biology of LUAD. Herein, a set of novel ncRNAs that include miRNAs, lncRNAs, circRNAs, were identified and differentially expressed patterns of ncRNAs and mRNAs in LSCs and ALDH- H1975 LUAD tumor cells (LTCs) were obtained using stringent bioinformatics pipelines. Through a meta-analysis of the identified landscapes, novel competitive endogenous RNA (ceRNA) networks were constructed to reveal the potential molecular mechanisms that regulate the hallmarks of LSCs and LTCs. This study presents a summary of novel ncRNAs and the fundamental roles of differentially expressed ncRNAs implicated in the activity of LSCs and LTCs. In addition, the study also provides a comprehensive resource for the future identification of diagnostic, therapeutic, and prognostic biomarkers in LUAD.