It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study.
Participant is willing and able to give informed consent for participation in the study;
Patients with new diagnosis and/or relapse/s of primary or secondary B-ALL;
Negative for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements;
Participant is willing and able to give informed consent for participation in the study;
Age < 18 years;
B-ALL positive for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements.
Patients diagnosed with Ph-/-/- B cell Acute Lymphoblastic Leukemia (see inclusion criteria) will be considered for enrolment. Therefore, patients can be enrolled at diagnosis or relapse/s. About 60 patients affected by primary or secondary B-ALL, at diagnosis and/or relapse/s will be enrolled in this study. All suitable prospective fresh PB and/or BM samples will be evaluated with cytofluorimetric panel.
Cohort
Prospective
"Triple negative" adul B-cell ALL
Other interventionSamples will be studied with conventional techniques to classify and define properly the disease: morphology, immunophenotype, immunohistochemistry (IHC), conventional Cytogenetic Fluorescence in Situ Hybridization (FISH) will be used when appropriate. ● Isolation of Mononuclear cells The following research methodologies will be applied: * Next Generation Sequencing * Flow cytometry analysis of 3C-up B-ALL top three markers * Gene expression profile analysis * Copy number Alterations analysis * In vitro studies
Biological characterization for B-ALL Ph-/-/- subgroup identification
Biological characterization of Ph-/-/- ALL, considering CRLF2 overexpression event, to better define clusters preliminarily identified and to identify biomarkers in these subgroups. Each sample at diagnosis and/or relapse time-point will be sequenced with an RNA-seq capture approach. Through bioinformatic analysis we will identify upregulated CRLF2 samples and associated gene signature. Fusion, mutation identification will integrate expression data.
Correlation, in terms of survival, between identified Ph-/-/- molecular subgroups and eventual novel associated molecular features.
To investigate the association of identified Ph-/-/- molecular subgroups and/or molecular features with the clinical outcome (OS, EFS). To assess if a Ph-/-/- molecular subgroups, identified thanks to our analyses, could be associated with poor prognosis.
Cytofluorimetric evaluation of Ph-/-/- ALL markers as CRLF2, CTGF and CD200.
To evaluate if the cytofluorimetric assay - developed on the basis of preliminary data - may be used to detect triple negative subgroups, to provide a rapid, simple and economically viable diagnostic tool to recognize these cases at presentation. On each enrolled fresh sample cells will be analysed through a B-ALL flow cytometer panel (e.g. CD45, CD19, CD34) to which markers of interest will be added (e.g. CRLF2, CTGF and CD200). Their expression in flow cytometry will be compared with the expression obtained from RNA-seq data.
Discover new biomarkers identified Ph-/-/- molecular subgroups
To assess if some molecular feature could be associated to specific Ph-/-/- molecular subgroups. To explore if these biomarkers, detected in some of identified Ph-/-/- molecular subgroups, could be targeted by novel drugs. To evaluate the drug/s effects through sensitivity in vitro/ex vivo tests on B-ALL cell lins and on primary leukemic cells.
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