Identification of a new subgroup of adult acute T-lymphoblastic leukemia (T-ALL) with a very favorable outcome using low ERG and BAALC expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7014-7014
Author(s):  
C. D. Baldus ◽  
P. Martus ◽  
T. Burmeister ◽  
S. Schwartz ◽  
N. Goekbuget ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Favorable Outcome ◽  
High Expression ◽  
Treatment Intensification ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Low Expression

7014 Background: High expression of the oncogenic ETS transcription factor ERG is an independent adverse prognostic factor in T-ALL and acute myeloid leukemia (AML). The gene BAALC similarly shows high expression in hematopoietic progenitors, downregulation with onset of differentiation, and prognostic significance in AML. Therefore, we assessed whether combined expression of ERG and BAALC would better predict outcome in T-ALL. Methods: ERG and BAALC mRNA expression was determined by realtime RT-PCR in pretherapy bone marrow of 152 adults with newly diagnosed T-ALL treated on German ALL protocols (05/93, 06/99). Patients (pts) were designated low (n=76) or high (n=76) ERG expressers based on median ERG expression and as low (n=111) or high (n=37) BAALC grouping the lower quartiles 1–3 vs. quartile 4. HOX11 and HOX11L2 expression was determined and immunophenotyping differentiated 3 T-ALL groups (early, thymic, mature). Results: High BAALC expression correlated with immature T-ALL with a higher frequency of early T-ALL (P<0.0001), CD34 positivity (P<0.0001), co-expression of myeloid markers (CD13 and/or CD33; P=0.03), and high ERG expression (P=0.02). Pts with high BAALC had fewer complete remissions (73% vs. 89%, P=0.03) and a higher relapse rate (67% vs. 32%, P=0.01) than low BAALC pts. Excluding 33 pts that had received stem cell transplantation (SCT), high expression of ERG (P=0.002) and of BAALC (P=0.0004) was associated with inferior relapse-free survival (RFS) and overall survival (OS, ERG: P=0.004; BAALC: P=0.0001) compared to low expression of ERG and BAALC, respectively. In contrast, pts with low expression of both ERG and BAALC had the most favorable outcome (5y-RFS: low ERG/low BAALC 81% vs. high ERG and/or high BAALC 33%, P<0.0001; 5y-OS: low ERG/low BAALC 69% vs. high ERG and/or high BAALC 26%, P=0.0001). On multivariable analysis low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, HR: 0.18, P=0.0003; OS, HR: 0.3, P=0.001); the only other prognostic factor was the immunophenotype. Conclusions: Low expression of both ERG and BAALC identifies T-ALL pts with a distinctly favorable long term outcome, thus detecting pts that may not benefit from further treatment intensification including SCT. No significant financial relationships to disclose.

LowERGandBAALCExpression Identifies a New Subgroup of Adult Acute T-Lymphoblastic Leukemia With a Highly Favorable Outcome

2007 ◽  
Vol 25 (24) ◽  
pp. 3739-3745 ◽  
Author(s):  
Claudia D. Baldus ◽  
Peter Martus ◽  
Thomas Burmeister ◽  
Stefan Schwartz ◽  
Nicola Gökbuget ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Favorable Outcome ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Polymerase Chain ◽  
Low Expression

PurposeExpression of the genes ERG (v-ets erythroblastosis virus E26 oncogene homolog) and BAALC (brain and acute leukemia, cytoplasmic) shows similarity during hematopoietic maturation and predicts outcome in acute myeloid leukemia. We hypothesized that like ERG, BAALC expression might be of prognostic significance in acute T-lymphoblastic leukemia (T-ALL) and that ERG and BAALC expression together would better identify the patient's risk profile.Patients and MethodsERG and BAALC mRNA expression were determined by real-time reverse transcriptase polymerase chain reaction in 153 adults with T-ALL. Patients were designated low or high ERG expressers and low or high BAALC expressers.ResultsHigh BAALC expression correlated with a higher frequency of early T-ALL (P < .0001), CD34 positivity (P < .0001), coexpression of myeloid markers (P = .0001), and high ERG expression (P = .03). High BAALC compared with low BAALC patients had an inferior relapse-free survival (RFS; P = .0008) and overall survival (OS; P = .0001). In contrast, patients with low expression of both ERG and BAALC (representing 41% of all T-ALL patients) had the most favorable outcome (P < .0001; 4-year RFS: low ERG/low BAALC 81%; P < .0001; 4-year OS: low ERG/low BAALC 69%). On multivariable analysis, low ERG/low BAALC expression was of independent favorable prognostic significance (RFS, P = .001; OS, P = .003).ConclusionLow expression of both ERG and BAALC identifies T-ALL patients with a distinctly favorable long-term outcome.

scholarly journals Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 967
Author(s):  
María I. Aroca-Siendones ◽  
Sara Moreno-SanJuan ◽  
Jose D. Puentes-Pardo ◽  
Michela Verbeni ◽  
Javier Arnedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Prognostic Significance ◽  
Developed Countries ◽  
Disease Diagnosis ◽  
Independent Prognostic Factor ◽  
High Expression ◽  
Incidence And Mortality ◽  
Circadian Clock Proteins ◽  
Low Expression

Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.

Immunophenotyping to Detect Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia - Feasibility and Prognostic Significance.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4489-4489
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Krystyna Jagoda ◽  
Malgorzata Krawczyk-Kulis ◽  
Beata Stella-Holowiecka ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Antigen Expression ◽  
Term Outcome ◽  
Long Term Outcome ◽  
B Lineage ◽  
Minimal Residual

Abstract Although well documented for pediatric patients, the prognostic value of minimal residual disease (MRD) detected with the use of immunophenotyping has not been established for adults with acute lymphoblastic leukemia (ALL) so far. With the use of standard “quadrans” analysis based on evaluation of the number of blasts bearing atypicial antigen combinations, the method may be applied to the majority of T-derived and only approximately half of B-lineage ALL. In this study we tested the feasibility and prognostic significance of a new “empty spaces” method taking into account the individual antigen expression pattern for each blast cell tested. The “forbidden” gates were established with the use of triple staining by comparison with the pattern obtained for healthy volunteer bone marrow donors. At least two antigen combinations were tested for each patient. MRD was evaluated after induction and after consolidation therapy. Only patients who achieved complete remission after a single course of induction were analysed with regard to the impact of MRD on long-term outcome. Thirty adult ALL patients (B-lineage n=24, T-lineage n=6) were included in the study. For all cases it was possible to determine unique antigen expression pattern and to monitor MRD with the use of immunophenotyping at the level of 1/1000 cells. MRD was detected in 8/30 patients after induction and in 7/28 patients after consolidation tharapy (two patients relapsed during consolidation). For 11/30 patients the MRD resulted positive at least once. At 20 months the relapse rate equaled 53% for patients with MRD detected after induction or consolidation and 28% for those with MRD always negative (p=0.08). The difference was more pronounced for patients with B-lineage ALL (67% vs. 26%, p=0.02). A single MRD evaluation after induction therapy had no significant prognostic value for the risk of relapse whereas there was a trend for higher relapse rate in B-lineage ALL patients with positive MRD after completion of consolidation therapy compared to those MRD-negative at that time-point (75% vs. 32%, p=0.06). Results of the study prove the feasibility of immunophenotypic MRD evaluation in ALL. “Empty spaces” in addition to the standard “quadrans” analysis allows monitoring of the vast majority of patients regardless the immune subtype. Even with a small number of cases we were able to demonstrate its prognostic value for long-term outcome of adults with ALL.

scholarly journals Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461

Blood ◽  
2006 ◽  
Vol 108 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Sherif S. Farag ◽  
Kellie J. Archer ◽  
Krzysztof Mrózek ◽  
Amy S. Ruppert ◽  
Andrew J. Carroll ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Acute Myeloid

We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex ≥ 3) and a group including “rare aberrations” predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex ≥ 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex ≥ 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex ≥ 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P < .001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex ≥ 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care. (Blood. 2006;108:63-73)

scholarly journals Prognostic significance of esterase gene expression in multiple myeloma

2021 ◽  
Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genomic Variation ◽  
High Expression ◽  
Genetic Profile ◽  
Esterase Gene ◽  
Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

scholarly journals Sarcopenia Is a Negative Prognostic Factor in Patients Undergoing Transarterial Chemoembolization (TACE) for Hepatic Malignancies

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1503 ◽  
Author(s):  
Loosen ◽  
Schulze-Hagen ◽  
Bruners ◽  
Tacke ◽  
Trautwein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Muscle Mass ◽  
Transarterial Chemoembolization ◽  
Cox Regression ◽  
Psoas Muscle ◽  
Muscle Size ◽  
Rapid Decline ◽  
Term Outcome ◽  
Long Term Outcome

: Background and Aims: While transarterial chemoembolization (TACE) represents a standard of therapy for intermediate-stage hepatocellular carcinoma (HCC) and is also routinely performed in patients with liver metastases, it is still debated which patients represent the ideal candidates for TACE therapy in terms of overall survival. Sarcopenia, the degenerative loss of skeletal muscle mass and strength, has been associated with an adverse outcome for various malignancies, but its role in the context of TACE has largely remained unknown. Here, we evaluated the role of sarcopenia on the outcome of patients undergoing TACE for primary and secondary liver cancer. Methods: The patients’ psoas muscle size was measured on axial computed tomography (CT) scans and normalized for the patients’ height squared. This value was referred to as the psoas muscle index (PMI). The PMI was correlated with clinical and laboratory markers. Results: While pre-interventional sarcopenia had no impact on the direct tumor response to TACE, sarcopenic patients with a pre-interventional PMI below our ideal cut-off value of 13.39 mm/m2 had a significantly impaired long-term outcome with a median overall survival of 491 days compared to 1291 days for patients with a high PMI. This finding was confirmed by uni- and multivariate Cox-regression analyses. Moreover, a progressive rapid decline in muscle mass after TACE was a predictor for an unfavorable prognosis. Conclusion: Our data suggest that sarcopenia represents a previously unrecognized prognostic factor for patients undergoing TACE therapy which might yield important information on the patients’ post-interventional outcome and should therefore be implemented into clinical stratification algorithms.

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