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This meta-analysis examined the prognostic role of brain and acute leukemia, cytoplasmic (BAALC), Ecotropic virus integration site-1 (EVI1) and Wilms' tumor 1 (WT1) genes at different time-points during conventional chemotherapy. A systematic search of publications indexed in the electronic databases from January 1988 to October 2020 was performed. Over 7525 cases of AML from 25 studies were involved. At diagnosis, overexpression of either BAALC or EVI1 had a negative impact on complete remission achievement (Summary Odds ratios [SORs] for BAALC = 0.32; SORs for EVI1 = 0.49) and survival outcome. The summary hazard ratios of overall survival (OS) and disease-free survival (DFS) were 1.97 and 2.04 for BAALC and 1.33 and 1.86 for EVI1, respectively. The prognostic value of pretreatment WT1 levels was heterogeneous while subgroup analyses unveiled that overexpressed WT1 may correlate with a favorable outcome (summary hazard ratio [SHR] for OS = 0.42). Both WT1 and BAALC played a role in prognosis assessment at post-induction and the diagnostic performance of WT1 transcript reduction was superior to the absolute WT1 level. Post-consolidation WT1 overexpression consistently indicated an increased risk of relapse, while the combined HR for RFS was statistically insignificant (SHR = 4.22). These findings confirm the application of BAALC and EVI1 at diagnosis, WT1 after induction chemotherapy in AML patients throughout conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. It possesses different cytogenetic and molecular features. The expression of Wilms tumor-1 (WT1), brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) might be considered as prognostic factors in AML patients. The aim of this study was to determine the mRNA expressions of WT-1, BAALC and ERG genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy. Methods: Forty AML patients with normal karyotype were evaluated. The mRNA gene expressions were measured with quantitative real-time PCR in bone marrow of mononuclear cells of AML patients at the baseline and after chemotherapy. The subtypes of AML and flow cytometry panel were also assessed. Complete remission (CR) after the treatment was addressed for all patients. Results: The mRNA expressions of WT-1, BAALC and ERG were significantly decreased after the treatment (p= 0.001, 0.017, 0.036). WT-1 mRNA expression was inversely correlated with CR after chemotherapy (P =0.024). There was also significant correlation between baseline expression of BAALC and CR (P=0.046). No significant correlation was observed between ERG and CR pre- and post- chemotherapy (P =0.464 and 0.781). There was also significant correlation between BAALC mRNA expression and CD34+ (P <0.001). Conclusion: The present study showed that WT-1 decreased significantly after standard chemotherapy which could have favorable effects on CR. Also, the high expression of BAALC could have a poor prognostic role in AML patients. The identification of these gene expressions can be an efficient approach in targeted therapy among AML patients. [ABSTRACT FROM AUTHOR]

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS‐related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease‐free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow‐up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001). [ABSTRACT FROM AUTHOR]

The aim of this work is to investigate the different expression patterns of B cell-specifics moloney murine Leukemia virus integration site-1 (BMI-1) and brain and acute leukemia, cytoplasmic (BAALC) genes, their prognostic and clinical significance in newly diagnosed cytogenetically heterogenous adult acute myeloid leukemia patients. BMI-1 and BAALC expression was detected in the bone marrow of patients using quantitative real-time reverse transcription polymerase chain reaction with cut off value set at 50th percentile for both genes. BMI-1 and BAALC overexpression was detected in 50% of cases which suggest their potential as molecular markers. A statistical significant correlation was found between BMI-1 expression with hepatomegaly (P value = 0.007), hemoglobin level-grouped (P value = 0.047) and cytogenetic risk groups (P value = 0.036). There was a statistically significant correlation between BAALC and age (P value = 0.015), lymphadenopathy (P value = 0.043), CD34 expression (P value = 0.003) and near statistical significance with FAB sub-groups (P value = 0.054). No statistical significance was noted for other hematological findings and response to treatment except for BAALC gene and treatment response (P value = 0.014). No statistical significance in overall survival and disease free survival for both genes was found. Their prospective screening in combination with other molecular markers can help refine myeloid leukemia staging and prognosis toward optimizing therapeutic interventions. [ABSTRACT FROM AUTHOR]

For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML. [ABSTRACT FROM AUTHOR]

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Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT. [ABSTRACT FROM AUTHOR]

Background:Brain and Acute Leukemia Cytoplasmic (BAALC) is a gene which its expression is confined to progenitor cells; therefore, no expression has been illustrated in mature cells of bone marrow or white blood cells (WBC). In addition, high BAALC expression is associated with poor prognosis in Acute Myeloid Leukemia (AML) individuals and is considered as an important risk factor in Cytogenetic Normal Acute Myeloid Leukemia. Materials and Methods: This retrospective study was designed to evaluate prognostic importance of BAALC gene expression in pediatric AML patients. Recently, recognized 114 AML Iranian children with age range of 1-15 years were entered in this study during 2012-2015. Real-Time PCR was applied for BAALC gene. Results: High BAALC gene expression was detected in 47 patients (41.2%) and low expression in 67 patients (58.8%). High BAALC gene expression group (n=47) contained23 males and 24 females. All patients were followed up for 2 years to measure disease prognosis. BAALC expression was a main unfavorable prognostic factor in AML patient's especially normal karyotype. AML cases with high BAALC expression had considerable further cumulative risk after 25 months; it was 39 months in low expressed cases. All of cytogenetic normal acute myeloid leukemias (CN-AML) and high BAALC expressed patients died. High BAALC expression in AML cases was associated with considerable shorter overall survival (OS). Conclusion: According to our findings, BAALC expression is a significance poor prognostic factor in AML patients with normal karyotype. This study suggests new therapeutic strategies to ameliorate the treat rate of AML patients. Further research with longer follow up and larger sample size is required to definite statistical perusals. [ABSTRACT FROM AUTHOR]

High BAALC gene expression has been associated with poor prognosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and has been suggested as a suitable marker for assessing minimal residual disease ( MRD). The purpose of this study was to substantiate these findings by the analysis of a large data set of 632 diagnostic and follow-up samples in 142 intensively treated CN- AML patients. Paired diagnostic/relapse samples of 35 patients revealed stable high BAALC expression in 89%, irrespective of a high proportion of clonal evolution found in 49% of these cases. High BAALC expression, both directly after induction chemotherapy and within 3-6 months after induction chemotherapy, correlated significantly with shorter event-free survival and overall survival. Moreover, 8 of 10 patients displaying high BAALC expression levels after completion of induction therapy as well as 5 of 5 patients exhibiting high BAALC expression levels within 3-6 months after induction chemotherapy experienced relapse with a median of 197 and 101 days, respectively, from sampling to relapse. Thus, BAALC expression-based MRD detection during therapy may be considered a strategy to identify patients at high risk of relapse. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a malignant disorder involving blood cells, characterized by obstructed or distorted differentiation of hematopoietic stem cells. In cytogenetically normal AML (CN AML), molecular abnormalities in NPM, FLT3, CEBPA, and BAALC genes are observed. Initially, high BAALC (Brain and Acute Leukemia Cytoplasmic gene) expression was introduced in a study on AML cases with trisomy 8. The present systematic review aimed to determine the prognostic value of BAALC expression in CN-AML patients within the age range of 1 month to 15 years. Materials and Methods: In this systematic review, scientific databases including PubMed, Scopus, Embase, ISI, and Cochrane Library were searched. All the evaluated retrospective studies focused on the prognostic value of BAALC expression. Results: Overall, BAALC expression was reported in 30-60% of AML patients (mean=45%). High expression of BAALC gene was reported in M0, M1, and M2 subtypes of pediatric AML. In only one study, in addition to these subtypes, M4 was also reported (12.5% of cases). Conclusion: This systematic review resulted in a significant association between high BAALC expression and poor response to chemotherapy in pediatric AML. However, OS (Overall Survival) and EFS (Event - Free Survival) findings were contradictory, relapse and death increase in the presence of high BAALC expression. Therefore, BAALC expression could be considered as a clinical prognostic marker for the treatment of AML patients. Further efficient prognostic indicators should be identified in order to gather information about therapeutic strategies for AML and risk analysis in these patients. [ABSTRACT FROM AUTHOR]

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45 % of de novo adult AML and 20 % of pediatric AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. Mutation status of FLT3, NPM1 genes and gene expression levels of ERG, BAALC have been postulated as possible prognostic markers in pediatric AML with normal karyotype. Pretreatment blood samples from 47 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression based on the median expression as cutoff. BAALC showed high expression in (24/47; 51.1 %) of patients and ERG high expression was detected in (22/47; 46.6 %). With follow-up for 1 year, patients with high BAALC and high ERG had inferior EFS ( P = 0.001, P = 0.017 respectively), overall survival ( P = 0.001, 0.08 respectively), and low rates of induction remission ( P = 0.001, P = 0.0017 respectively) as compared to those with low expression. Also there was significant positive association between high expression of BAALC; ERG and FLT-ITD mutations ( P = 0.016; P = 0.007 respectively). Multivariable analysis confirmed that high BAALC expression is an independent risk factor for EFS [HR for EFS 1.9(1.04-3.46) P = 0.037]; and OS [HR OS 1.55(1.7-3.36) P = 0.03]. In conclusion: Over expression of BAALC could predict adverse clinical outcome and may define important risk factor in cytogenetically normal pediatric AML. [ABSTRACT FROM AUTHOR]

To investigate the expression of brain and acute leukemia, cytoplasmic ( BAALC) and analyze its clinical significance in Chinese de novo acute myeloid leukemia (AML). Real-time quantitative PCR (RQ-PCR) was carried out to detect BAALC transcript level in 121 de novo AML patients and 41 normal controls. BAALC transcript level in AML patients was significantly up-regulated compared with normal controls ( P < 0.001). Patients with high BAALC expression had significantly older age than those with low BAALC expression ( P = 0.021). The percentage of blasts in bone marrow of the BAALC high-expressed patients was significantly higher than that in the low-expressed patients ( P < 0.001). The incidence of BAALC overexpression was significantly higher in M0/M1 (8/9, 89 %) and M2 subtypes (33/48, 68 %) than in M3 subtype (6/27, 22 %) ( P < 0.001). The frequency of IDH1/2 wild type in CN-AML patients with high BAALC expression was significantly higher than those with low BAALC expression ( P = 0.031). BAALC high-expressed patients had a significantly lower complete remission than low-expressed patients in both entire AML cohort and CN-AML ( P = 0.013 and 0.029, respectively). Furthermore, both whole AML cohort and CN-AML patients with high BAALC expression showed a shorter overall survival than those with low BAALC expression ( P = 0.002 and 0.008, respectively). Multivariate analysis confirmed high BAALC expression as an independent adverse prognostic factor in both AML and CN-AML patients. Our study indicates that overexpression of BAALC serves as an independent prognostic biomarker in both whole AML cohort and CN-AML patients. [ABSTRACT FROM AUTHOR]

Data for 125 patients with cytogenetically normal acute myeloid leukemia (CN-AML) regarding BAALC and combinatorial molecular markers at diagnosis were evaluated. Fewer patients with higher BAALC expression at diagnosis achieved a complete remission (CR) (49.2 vs. 75.8%, p = 0.002) after the first cycle of chemotherapy, and there were more primary refractory cases (37.3 vs. 18.2%, p = 0.017). In a combinatorial analysis, FLT3-ITD-positive patients with higher BAALC showed more refractoriness and the worst overall survival (OS) ( p < 0.001) and disease-free survival (DFS) ( p < 0.001) in CN-AML. When NPM1-mutated CN-AML was combined with either FLT3-ITD mutation or higher BAALC expression, both OS ( p = 0.043) and DFS ( p = 0.008) were worse; when combined with both, it showed the worst OS ( p < 0.001) and DFS ( p = 0.004). Higher BAALC expression and FLT3-ITD mutation, both individually and in combination, were associated with worse survival outcomes in CN-AML, and this was also applicable in NPM1-mutated CN-AML, known as a favorable-risk group. [ABSTRACT FROM AUTHOR]

Objective: We performed comprehensive proteomic analyses of articular cartilage by using the isobaric tags for relative and absolute quantitation (iTRAQ) method, and searched for candidate biomarkers for osteoarthritis (OA). Methods: Articular cartilage was collected from patients with OA or femoral neck fracture for the control group. Molecular variations were detected by the ITRAQ method, and quantitative analyses were performed by western blot. Results: Using the iTRAQ method, we identified 76 proteins with different expression levels in OA patients and the control group. Among these proteins, we selected LECT2 (leukocyte cell-derived chemotaxin-2), BAALC (brain and acute leukemia, cytoplasmic), and PRDX6 (peroxiredoxin-6), which had not been reported as biomarkers for OA. Conclusions: Use of these proteins in combination with conventional OA biomarkers may better reflect the grade and prognosis of OA. [ABSTRACT FROM AUTHOR]

No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML ( CBF- AML) from diagnosis to hematopoietic stem cell transplantation ( HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction ( RQ- PCR) at diagnosis, after induction chemotherapy, at pre- HSCT, and at post- HSCT period in 45 consecutive patients [t(8,21) ( n = 28), inv(16) (n = 17)], who received HSCT as a post-remission treatment. BAALC and WT1 RQ- PCR decrement ratio ( DR) was also calculated at post-induction chemotherapy, at pre- HSCT, and at post- HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS ( P = 0.031), EFS ( P = 0.011), and higher CIR ( P = 0.002) rates. At post- HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS ( P = 0.005, 0.016), EFS ( P = 0.002, 0.006), and higher CIR ( P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post- HSCT were also associated with inferior OS ( P = 0.018, 0.015) and higher CIR rates ( P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post- HSCT showed significantly lower CIR rate ( P = 0.028). This study showed that higher post- HSCT BAALC and WT1 expressions in patients with CBF- AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. [ABSTRACT FROM AUTHOR]

Brain and acute leukemia, cytoplasmic (BAALC) is a novel molecular marker indicating an inferior outcome in acute myeloid leukemia (AML) with normal cytogenetics. The biological function of BAALC is largely unknown. In this study, BAALC gene expression in an acute myeloid leukemia cell line KG1a was knocked down by a small hairpin RNA (shRNA). The expression of BAALC mRNA and protein in the knockdown cells was significantly inhibited. The proliferation and apoptosis status in the knockdown cells were investigated. The growth curves and FACS analysis demonstrated that BAALC gene knockdown resulted in decreased proliferation and enhanced apoptosis in KG1a cells. These results indicated that BAALC may act as an adverse prognostic factor through prompting proliferation and inhibiting apoptosis in leukemia cells. [ABSTRACT FROM AUTHOR]

We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracycline-AraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 ( p == 0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age ( p == 0.00009), NPM gene mutation ( p == 0.002), and WT1 >75th percentile (>2365) ( p == 0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients ( p == 0.003 and p == 0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype ( p == 0.008 and p == 0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30%% vs. 6%% in FLT3-ITD negative and FLT3 positive patients, respectively; p == 0.01) and OS (OS at 30 months: 38%% vs. 20%%, p == 0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy. [ABSTRACT FROM AUTHOR]

Over expression of BAALC (brain and acute leukemia, cytoplasmic) predicts an inferior outcome in acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients. To identify BAALC-associated genes that give insights into its functional role in chemotherapy resistance, gene expression signatures differentiating high from low BAALC expressers were generated from normal CD34+ progenitors, T-acute lymphoblastic leukemia (T-ALL) and AML samples. The insulin-like growth factor binding protein 7 (IGFBP7) was one of the four genes (CD34, CD133, natriuretic peptide receptor C (NPR3), IGFBP7) coexpressed with BAALC and common to the three entities. In T-ALL, high IGFBP7-expression was associated with an immature phenotype of early T-ALL (P<0.001), expression of CD34 (P<0.001) and CD33 (P<0.001). Moreover, high IGFBP7-expression predicted primary therapy resistance (P=0.03) and inferior survival in T-ALL (P=0.03). In vitro studies revealed that IGFBP7 protein significantly inhibited the proliferation of leukemia cell lines (Jurkat cells: 42% reduction, P=0.002; KG1a cells: 65% reduction, P<0.001). In conclusion, IGFBP7 was identified as a BAALC coexpressed gene. Furthermore, high IGFBP7 was associated with stem cell features and treatment failure in T-ALL. In contrast to BAALC, which likely represents only a surrogate marker of treatment failure in acute leukemia, IGFBP7 regulates the proliferation of leukemic cells and might be involved in chemotherapy resistance. [ABSTRACT FROM AUTHOR]

High BAALC (brain and acute leukemia, cytoplasmic) gene expression may indicate an adverse prognosis for adults who have acute myeloid leukemia (AML) and a normal karyotype, but its prognostic significance for pediatric AML cases is unclear. Whether different BAALC isoform patterns are of prognostic significance is also unclear. Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49). Eleven and 18 patients exhibited high and low BAALC expression, respectively, but these groups did not differ significantly in terms of overall survival (54.6 vs. 61.1%, P = 0.55) or event-free survival (61.4 vs. 50.0%, P = 0.82). Three of these 29 patients (10.3%) expressed the exon 1-5-6-8 BAALC isoform along with the expected 1-6-8 isoform and had adverse clinical outcomes. Novel CEBPA mutations were also identified in four of 49 patients (8.2%). All four patients have maintained complete remission for at least 5 years. Thus, 1-5-6-8 isoform expression may be associated with an adverse prognosis in pediatric AML with normal karyotype. CEBPA mutations may indicate a favorable prognosis. [ABSTRACT FROM AUTHOR]

We have analyzed brain and acute leukemia, cytoplasmic ( BAALC) gene expression and other genetic markers ( ERG, EVI1, MN1, PRAME, WT1, FLT3, and NPM1 mutations) in 127 intermediate-risk acute myeloid leukemia (AML) patients: 98 cytogenetically normal and 29 with intermediate-risk cytogenetic alterations. High versus low BAALC expressers showed a higher refractoriness to induction treatment (31% vs 10%; p = .005), lower complete remission rate after salvage therapy (82% vs 97%; p = .010), and lower 3-year overall (23% vs 58%, p < .001) and relapse-free survival (26% vs 52%, p = .006). Similar results were found when cytogenetic subgroups were analyzed separately. Multivariate models confirmed the unfavorable prognosis of this marker. In conclusion, BAALC is a relevant prognostic marker in intermediate-risk AML. [ABSTRACT FROM AUTHOR]

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45% of de novo AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. We studied the prognostic impact of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression in AML with normal karyotype. Pretreatment bone marrow samples from 30 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression. BAALC showed high expression in 70% of patients and its expression did not correlate with the clinical parameters of patients. ERG was high in 33.3% of patients and its expression was associated with lower ages and higher white cell counts. With follow-up for 2 years, patients with high BAALC and high ERG had low rates of clinical remission ( P < 0.005) and inferior overall survival (OS) ( P < 0.001 and <0.002 for BAALC and ERG respectively). No significant association was observed between the increase in BAALC and ERG expression ( P = 0.398). Multivariable analysis confirmed high BAALC expression as an independent risk factor for OS. Overexpression of BAALC and ERG either separate or concomitant predict adverse clinical outcome and may define important risk factor in cytogenetically normal AML. [ABSTRACT FROM AUTHOR]

Abstract: Genes controlling proliferation and differentiation of astrocytes are likely to play an important role in the pathogenesis of astrocytic gliomas and could serve as therapeutic targets. mRNA differential display analysis identified two genes, viz. BAALC and RAMP3, whose expression is altered in primary astrocytes treated with differentiation inducers. BAALC, which has been reported to be expressed in neural progenitor cells, was found to be up regulated in both normal and malignant astrocytes on inhibition of proliferation. RAMP3 functions as a modulator of the receptor for adrenomedullin (AM). AM has been suggested to act as autocrine/paracrine growth factor for gliomas. Our studies show RAMP3 down regulation on staurosporine treatment of astrocytes, suggesting protein kinase C inhibition as a possible strategy for inhibiting AM activity and thereby growth of glioma cells. [Copyright &y& Elsevier]