Bone Marrow Stromal Cell Regeneration Profile in Treated B-Cell Precursor Acute Lymphoblastic Leukemia Patients: Association with MRD Status and Patient Outcome.

For the last two decades, measurable residual disease (MRD) has become one of the most powerful independent prognostic factors in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the effect of therapy on the bone marrow (BM) microenvironment and its potential relationship with the MRD status and disease free survival (DFS) still remain to be investigated. Here we analyzed the distribution of mesenchymal stem cells (MSC) and endothelial cells (EC) in the BM of treated BCP-ALL patients, and its relationship with the BM MRD status and patient outcome.

Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols.

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients.

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified.

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL).

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study.

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.

Molecular profiling refines minimal residual disease-based prognostic assessment in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia.

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high-risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome-negative B-cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols.

Increased survival due to lower toxicity for high-risk T-cell acute lymphoblastic leukemia patients in two consecutive pediatric-inspired PETHEMA trials.

Objective And Methods: Pediatric-inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T-cell ALL. We analyzed 169 patients with high-risk T-cell ALL included in two consecutive trials of the PETHEMA Group (HR-ALL03 [n = 104] and the more contemporary HR-ALL11 [n = 65]).

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL.

Altered neutrophil immunophenotypes in childhood B‑cell precursor acute lymphoblastic leukemia.

An increasing number of evidences suggest a genetic predisposition in acute lymphoblastic leukemia (ALL) that might favor the occurrence of the driver genetic alterations. Such genetic background might also translate into phenotypic alterations of residual hematopoietic cells. Whether such phenotypic alterations are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL remains to be investigated.

Tumor infiltrating immune cells in gliomas and meningiomas.

Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood.

Identification of a characteristic copy number alteration profile by high-resolution single nucleotide polymorphism arrays associated with metastatic sporadic colorectal cancer.

Background: Metastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identification of patients with sCRC who are at risk of developing metastases.

Methods: The authors used high-resolution, 500-K single nucleotide polymorphism arrays to identify copy number alteration profiles present at diagnosis in primary tumors from patients with metastatic (n = 23) versus nonmetastatic (n = 26) sCRC.

Flow cytometry immunophenotyping of fine-needle aspiration specimens: utility in the diagnosis and classification of non-Hodgkin lymphomas.

Aims: To establish the utility of flow cytometry (FCM) for screening and diagnosis of B cell non-Hodgkin lymphoma (B-NHL) from lymphoid tissue samples obtained by fine-needle aspiration (FNA).

Methods And Results: We compared prospectively FCM versus cytology/histology analysis of FNA samples for the diagnostic screening and further World Health Organization (WHO) subclassification of B-NHL. FCM and cytology showed a high degree of agreement (93%); however, diagnosis of reactive processes (RP), B-NHL and T-NHL by FCM showed higher sensitivity than cytology (92-100% versus 64-94%, respectively), without false positive NHL cases.

The cytogenetic relationship between primary and recurrent meningiomas points to the need for new treatment strategies in cases at high risk of relapse.

Purpose: Recurrence is the major factor influencing the clinical outcome of meningioma patients although the exact relationship between primary and recurrent tumors still needs to be clarified. The aim of the present study is to analyze the cytogenetic relationship between primary and subsequent recurrent meningiomas developed within the same individual.

Experimental Design: Multicolor interphase fluorescence in situ hybridization was done for the identification of numerical abnormalities of 12 chromosomes in single-cell suspensions from 59 tumor samples corresponding to 25 recurrent meningioma patients.

Evaluation of multiparameter flow cytometry for the detection of breast cancer tumor cells in blood samples.

We comparatively evaluated different cytokeratin (CK) reagents analyzed by flow cytometry (FCM) for the identification of the best combination of DNA/CK staining for detecting minimal numbers of breast cancer cells in peripheral blood (PB). In 59 primary breast cancer tumors, we comparatively analyzed the reactivity for up to 6 different anti-CK reagents using multiparameter FCM: anti-CK7, anti-CK20, anti-pan-CK, anti-CK8/CK18, anti-CK8, and anti-CK18. Afterward, dilutional experiments of Michigan Cancer Foundation (MCF)7 breast cancer cells in PB were performed, and the sensitivity of a DNA/CK18 staining was evaluated.

Intratumoral patterns of clonal evolution in meningiomas as defined by multicolor interphase fluorescence in situ hybridization (FISH): is there a relationship between histopathologically benign and atypical/anaplastic lesions?

Meningiomas are cytogenetically heterogeneous tumors in which chromosome gains and losses frequently occur. Based on the intertumoral cytogenetic heterogeneity of meningiomas, hypothetical models of clonal evolution have been proposed in these tumors which have never been confirmed at the intratumoral cell level. The aim of this study was to establish the intratumoral patterns of clonal evolution associated with chromosomal instability in individual patients as a way to establish tumor progression pathways in meningiomas and their relationship with tumor histopathology and behavior.

Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value.

Investigation of minimal residual disease (MRD) in acute leukemias by immunophenotyping and/or molecular techniques is proving to be increasingly valuable for disease monitoring. In acute lymphoblastic leukemia (ALL), most MRD studies have focused on children, whereas in contrast, information on the value of MRD on adult ALL is scanty, and almost exclusively restricted to polymerase chain reaction (PCR) studies. Early response to therapy is one of the most important prognostic factors in acute leukemia, which prompted us to investigate whether or not early immunophenotypic assessment of MRD could also be a valuable tool for predicting relapse in adult patients with ALL.

Flow cytometry measurement of the DNA contents of G0/G1 diploid cells from three different teleost fish species.

Background: Although there is a lot information in the literature about genome size in fish, a high variability among data for the same species is reported, being mainly related to methodological aspects. Flow cytometry-based fluorescence measurements of intercalating dyes is the most attractive approach due to its precision, objectivity, high speed, and relative simplicity.

Methods: We analyze the DNA content of G0/G1 diploid nuclei of three teleost species (Carassius auratus, Tinca tinca, and Danio rerio) using flow cytometry.

Quantitative evaluation of the distribution of proliferating cells in the adult retina in three cyprinid species.

In the present study, a descriptive and quantitative analysis of all the proliferating cell populations present in the normal adult retina of three cyprinid species (goldfish, zebrafish, and tench) is reported. Evaluation of cell proliferation was performed in proliferating cell nuclear antigen (PCNA)-labeled tissue sections as well as in single-cell suspensions analyzed by flow cytometry. Our results show that the neural progenitors of the inner nuclear layer (INL) of cyprinids continue dividing in adulthood in uninjured retinas.