Prognostic stratification improvement by integrating ID1/ID3/IGJ gene expression signature and immunophenotypic profile in adult patients with B-ALL

Abstract

BackgroundSurvival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction.MethodsTo improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples.ResultsBoth techniques were correlated to stratify patients into prognostic groups. An inverse relationship between survival and expression of the three-genes signature was observed and an immunophenotypic profile associated with clinical outcome was identified. Markers CD10 and CD20 were correlated with simultaneous overexpression of ID1, ID3 and IGJ. Patients with simultaneous expression of the poor prognosis gene signature and overexpression of CD10 or CD20, had worse Event Free Survival and Overall Survival than patients who had either the poor prognosis gene expression signature or only CD20 or CD10 overexpressed.ConclusionBy utilizing the combined evaluation of these two immunophenotypic markers along with the poor prognosis gene expression signature, the risk stratification can be significantly strengthened. Further studies including a large number of patients are needed to confirm these findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0506-4) contains supplementary material, which is available to authorized users.

Id1 and Id3 Are Regulated Through Matrix‐Assisted Autocrine BMP Signaling and Represent Therapeutic Targets in Melanoma

“…This suggests that therapeutic targeting of Id1 and Id3, which is upregulated in the cancer context through either matrix-assisted autocrine regulation or through other mechanisms, may be more broadly applicable across different tumor types. Cancer entities reported to exhibit increased Id1 and/or Id3 levels that correlate with poor survival include prostate cancer, [48] B-acute lymphoblastic leukemia, [49] non-small cell lung cancer, [50] ovarian cancer, [51] esophageal squamous cell carcinoma, [52] and breast cancer. [53] In many cases, Id1 and Id3 are co-expressed in tumor tissues.…”

Study of body fluid samples using flow cytometry: Six years of experience at the Hospital Universitario San Ignacio - Pontificia Universidad Javeriana Bogota - Colombia

“…These advances have significantly improved minimal residual disease (MRD), detection, assessing therapy response. Moreover, it is considered an important prognostic indicator [18].…”

Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

“…While Id3 seems to play a tumor suppressor role in GC B cells that give rise to BL and perhaps GC B DLBCL, it may play oncogenic roles in other subtypes of B cell lymphomas. For instance, high expression of Id1 and Id3 genes in B cell adult lymphoblastic leukemia (B-ALL) leads to poor prognosis in adult patients [70]. Id4 has also been found to be overexpressed as a result of a translocation in B-ALL [71].…”