Correlation of Altered Expression of RIZ1 to Diagnosis, Risk Stratification, and Disease Progression in 56 Acute Leukemia Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2627-2627
Author(s):  
Qiubai Li ◽  
Xiaojian Zhu ◽  
Xiaoqing Li ◽  
Xiangjun Chen ◽  
Yong You ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Complete Remission ◽  
Risk Stratification ◽  
Acute Leukemia ◽  
Disease Progression ◽  
De Novo ◽  
Disease Risk ◽  
Lymphoblastic Leukemia ◽  
Altered Expression ◽  
Healthy Donors

Abstract Abstract 2627 Poster Board II-603 RIZ1 expression is altered in a variety of human cancers and is now considered to be a candidate tumor suppressor in many types of human tumors, including breast cancer, liver cancer, colon cancer, neuroblastoma, melanoma, lung cancer, and osteosarcoma. Previous studies indicate that suppression of RIZ1 expression may have an important role in leukemogenesis and RIZ1 is downregulated during CML progression and displays tumor suppressor properties in CML cell lines. To deeply investigate the expression of RIZ1 and its correlation to diagnosis, risk stratification, and disease progression in human acute leukemia, we analysed the differential expression of RIZ1 by quantitative real-time reverse-transcription polymerase chain reaction assay in 56 acute patients with or without complete remission and in 9 healthy donors. Our results showed that the expression of RIZ1 was significantly decreased in both de novo acute leukemia patients and patients with no remission (n = 35) (P = 0.009, compared with healthy donors) and significantly increased in acute leukemia patients with complete remission (P = 0.001, compared with de novo acute leukemia patients and patients with no remission). When compared with healthy donors, acute leukemia patients with complete remission (n = 21) owned the statistically same expression of RIZ1 (P = 0.595). The expression of RIZ1 was significantly higher in acute myeloid leukemia (AML, n = 17) than acute lymphoblastic leukemia (ALL, n =15) (P = 0.009), with a good correlation to diagnosis of AML or ALL (r = 0.514). The patients (n = 16) with high-risk leukemia had significantly higher expression of RIZ1 than the patients with standard-risk (n = 18) (P = 0.031), with the correlation (r = 0.431) of RIZ1 expression to disease risk-stratification. In addition, the weak correlations of RIZ1 expression were shown to both age and gender ( r = 0.158 and 0.003, respectively). This relatively simple analysis provides an important role of RIZ1 expression in acute leukemia. Taken together, our results suggest the potential for using RIZ1 expression in predication of disease progression or recovery in acute leukemia. We demonstrate that RIZ1 expression can contribute to the diagnosis of AML or ALL and the evaluation of risk-stratification in acute leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Overexpression of Cysteine and Glycine-Rich Protein 2 in Bone Marrow As a Novel Biomarker in Adult B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5271-5271 ◽  
Author(s):  
Shu-Juan Wang ◽  
Wei-Min Wang ◽  
Wen-Yi Lu ◽  
Ya-Zhen Qin ◽  
Yue-Yun Lai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
B Cell ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Serial Dilution ◽  
Newly Diagnosed ◽  
Healthy Donors ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Glycine Rich Protein

Abstract Background: Cysteine and glycine-rich protein 2 (CSRP2), a member of the CSRP family, is reported to be upregulated in highly invasive breast cancer cells and promote breast cancer cell invasiveness. The expression and clinical implications of CSRP2 have not been explored in B-cell acute lymphoblastic leukemia (ALL). Aims: To investigate the expression of human CSRP2 messenger RNA and explore its clinical implications in adult B-cell ALL. Methods: TaqMan fluorescent real-time quantitative polymerase chain reaction (qPCR) was used to quantify CSRP2 mRNA copy number in bone marrow samples from patients with B-cell ALL and control normal bone marrow samples from healthy allogeneic stem cell transplantation donors (HD). Results: CSRP2 was expressed at significantly higher levels in 232 newly-diagnosed B-cell ALL marrow samples (ND; median 63.8%; range 0-1368.1%) than 43 HD samples (median 0.4%; range 0-1.8%; P<0.001; Fig. 1A); at lower levels in 172 adult B-cell ALL samples (median 58.1%; range 0-1066.1%) than 60 pediatric B-cell ALL samples (median 93.0%; range 0-1368.1%; P=0.02; Fig. 1B); at lower levels in 206 complete remission samples (CR; median 0.8%; range 0-135.0%) than ND samples (P<0.001; Fig. 1C); and at comparable levels in 27 relapsed samples (median 90.9%; range 0.2-716.3%), 17 refractory samples (median 60.8%; range 2.9-548.5%) and ND samples (P>0.05; Fig. 1C). Minimal residual disease (MRD) was assessed by flow cytometry (FCM) in 166 CR samples: CSRP2 expression was significantly lower in the MRD <0.01% group (n=129, median 0.60%, range 0-18.9%) than MRD >0.01% group (n=37, median 3.2%, range 0.1-45.5%; P<0.001; Fig. 1D). Regarding to the association of CSRP2 transcript levels with clinical variables of adult B-cell ALL, patients with MLL rearrangement expressed remarkably higher CSRP2 levels while patients with complex karyotype expressed significantly lower CSRP2 levels than the other subgroups (Fig. 1E). There was no significant association of CSRP2 transcript levels with age, sex, WBC levels, bone marrow blasts or risk group (P>0.05). Longitudinal analysis was performed using 224 marrow samples from 50 patients with B-cell ALL; 27 patients expressed known fusion-gene transcripts (BCR-ABL, n=20; MLL-AF4, n=7) and 23 lacked additional molecular markers. Patients who achieved CR showed significant reductions in CSRP2 during follow-up; patients in relapse exhibited higher CSRP2 expression (Fig. 1F). In a subset of 182 samples, MRD estimates by FCM were also available. Using the threshold of 0.01% to define MRD positivity by FCM and 1.8% to define MRD positivity by CSRP2, there was a good correlation in the MRD-positive estimates by the 2 methods [r=0.751, 95%CI (0.523-0.885); P<0.0001; Fig. 1G]. Furthermore, we measured MRD using CSRP2 compared with BCR-ABL by qPCR in triplicate using standards made by serial dilution (10-1, 10-2, 10-3, 10-4, 10-5) of diagnosis cDNA from 7 patients and the close concordance of results was confirmed by the Spearman coefficient of rank correlation of 0.933 [95% CI (0.879-0.954); P<0.0001; Fig. 1H]. Conclusion: CSRP2 may serve as a novel biomarker and provide a potentially effective clinical indicator for auxiliary diagnosis and monitoring treatment efficacy in adult B-cell ALL. Figure A-F: CSRP2 expression in bone marrow samples from (A) newly-diagnosed (ND) B-cell ALL and healthy donors (HD); (B) adult and childhood B-cell ALL; (C) ND adult B-cell ALL, and patients with complete remission (CR), relapsed and refractory B-cell ALL; (D) patients with MRD determined by FCM <0.01% and >0.01% in patients with CR; (E) ND adult B-cell ALL with different karyotypes; (F) nine patients with de novo disease who experienced CR and then relapsed. G: Correlation between MRD monitored by CSRP2 and that monitored by FCM. H: Correlation between MRD monitored by CSRP2 and that monitored by BCR-ABL in serial dilution of diagnosis cDNA. *: P<0.05; **: P<0.01; ***: P<0.001. Figure. A-F: CSRP2 expression in bone marrow samples from (A) newly-diagnosed (ND) B-cell ALL and healthy donors (HD); (B) adult and childhood B-cell ALL; (C) ND adult B-cell ALL, and patients with complete remission (CR), relapsed and refractory B-cell ALL; (D) patients with MRD determined by FCM <0.01% and >0.01% in patients with CR; (E) ND adult B-cell ALL with different karyotypes; (F) nine patients with de novo disease who experienced CR and then relapsed. G: Correlation between MRD monitored by CSRP2 and that monitored by FCM. H: Correlation between MRD monitored by CSRP2 and that monitored by BCR-ABL in serial dilution of diagnosis cDNA. *: P<0.05; **: P<0.01; ***: P<0.001. Disclosures No relevant conflicts of interest to declare.

scholarly journals PIM2 and NF-κβ gene expression in a sample of AML and ALL Egyptian patients and its relevance to response to treatment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shymaa Kamal El Din Abed El Rahman ◽  
Sanaa Sayed Abd Elshafy ◽  
Mohamed Samra ◽  
Hala Mohammed Ali ◽  
Rabab Afifi Mohamed
Keyword(s):  
Overall Survival ◽  
Acute Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Expression Level ◽  
Response To Treatment ◽  
Control Group ◽  
Poor Overall Survival ◽  
Healthy Control ◽  
Complete Blood Counts

Abstract Background The relation between PIM2 and the transcriptional factor NF κβ have been controversial in literature. The significance of PIM2 and NF-κβ genes expression on the incidence of acute leukemia (AML and ALL) and its relevance to the response rate was evaluated. Sixty de novo acute leukemia patients were stratified in 2 groups: 30 acute myeloid leukemia (AML) and 30 acute lymphoblastic leukemia (ALL) patients and compared to 30 sex- and age-matched controls. The expression level of PIM2 and NF κβ genes was measured using quantitative real-time polymerase chain reaction (QRT-PCR). The patients were followed with clinical examination and complete blood counts. Results The expression level of PIM2 gene was significantly higher in AML patients (P<0.001) compared to the control group. The mean expression level of NF κβ gene was significantly high in AML and ALL patients compared to the healthy control group (P=0.037 and P<0.001; respectively). The overall survival in AML patients was higher in NF κβ gene low expressers compared to high expressers (P=0.047). The number of AML patients who achieved complete remission was significantly higher in PIM2 gene low expressers in comparison to PIM2 gene high expressers (P=0.042). Conclusion PIM2 and NF κβ genes might have a role in the pathogenesis of acute leukemia, poor overall survival, and failure of response to induction therapy.

FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies

2018 ◽  
Vol 25 (8) ◽  
pp. 1831-1838 ◽  
Author(s):  
Omima Mustafa ◽  
Khalid Abdalla ◽  
Aeshah A AlAzmi ◽  
Naglla Elimam ◽  
Mohammed Burhan Abrar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Salvage Therapy ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematologic Toxicity ◽  
Novel Therapies

Background Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies. Methods This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded. Result Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001). Conclusion Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.

scholarly journals Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction [see comments]

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2348-2353 ◽  
Author(s):  
S Kojima ◽  
T Matsuyama ◽  
T Sato ◽  
K Horibe ◽  
S Konishi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Electron Microscopic ◽  
Normal Children ◽  
Response To Chemotherapy

Abstract The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet- specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.

scholarly journals Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2920-2928 ◽  
Author(s):  
DS Snyder ◽  
NJ Chao ◽  
MD Amylon ◽  
J Taguchi ◽  
GD Long ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Total Body ◽  
First Complete Remission

Abstract Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

scholarly journals Expression of the multidrug resistance-associated P-glycoprotein (P- 170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications [see comments]

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2394-2398 ◽  
Author(s):  
JE Goasguen ◽  
JM Dossot ◽  
O Fardel ◽  
F Le Mee ◽  
E Le Gall ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Glycoprotein P ◽  
Kaplan Meier ◽  
Prognostic Implications ◽  
First Complete Remission

Abstract Immunocytochemical detection of the multidrug resistance (MDR)- associated membrane protein (P-170) was performed at time of diagnosis in a series of 36 children and 23 adults with acute lymphoblastic leukemia (ALL) using two monoclonal antibodies JSB1 and C219. Immunophenotypes were obtained in all cases and karyotypes were analyzed in 37 cases. Detection with JSB1 or with C219 led to similar results in terms of positive cells and cases, but the intensity of staining was higher with JSB1. In the populations studied, the rate of first complete remission differed between MDR-positive and MDR-negative in adult patients only (56% v 93%, respectively, P = .05). Of the 16 MDR-positive patients who had presented a first complete remission, 13 (81%) relapsed, compared with 13 of 35 (37%) MDR-negative (P = .008) patients. A higher rate of relapse among MDR-positive compared with MDR- negative patients was observed in adults and in children taken separately (adults 100% v 46%; children 73% v 32%, respectively). The survival rates (Kaplan-Meier method) were significantly higher in MDR- negative compared with MDR-positive populations as a whole (P = .002) and among children (P = .05) and adults (P = .03) taken separately. Event-free survival curves followed this trend. The percentage of second complete remission was very low in the MDR-positive group (15%) compared with 38% for the MDR-negative group. These results were shown by multivariate analysis to be independent of age, immunophenotypes, and karyotypes and clearly show the importance of MDR phenotype detection in ALL.

The Reliability and Specificity of c-kit for the Diagnosis of Acute Myeloid Leukemias and Undifferentiated Leukemias

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 596-599 ◽  
Author(s):  
M.C. Bene ◽  
M. Bernier ◽  
R.O. Casasnovas ◽  
G. Castoldi ◽  
W. Knapp ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Specific Marker ◽  
Acute Leukemias ◽  
Routine Basis ◽  
Immunological Classification ◽  
B Lineage ◽  
Acute Myeloid

Abstract We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T–ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

Enhanced Bacteriocidal Function by WKYMVm in Patients with Acute Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3844-3844
Author(s):  
Hawk Kim ◽  
Soojin Shin ◽  
Jae-Hoo Park ◽  
Eui-Kyu Noh ◽  
Young Joo Min
Keyword(s):  
Complete Remission ◽  
Acute Leukemia ◽  
Normal Control ◽  
Lymphoblastic Leukemia ◽  
Base Line ◽  
Consolidation Chemotherapy ◽  
Mean Values ◽  
Blast Count ◽  
Bactericidal Activities ◽  
Wbc Count

Abstract Acute leukemia (AL) is a disease of challenge in that many patients die not only from eventual relapse but also from infection during treatment. In this regard efforts for decreasing infectious mortality will help increasing survival. Our previous study revealed that leukocyte bacteriocidal functions in chemotherapy-treated cancer patients were decreased and were stimulated by a novel hexapeptide, WKYMVm. We evaluated the leukocyte bacteriocidal function in patients with AL and searched whether WKYMVm can enhance the bacteriocidal function in patients with AL. On induction chemotherapy, blood sampling was performed at diagnosis and repeated weekly from start day of chemotherapy until patient died or complete remission was achieved. Tests were done weekly until white blood cell (WBC) count reached up to 1000/mm3 and platelet counts were stable without transfusion after consolidation chemotherapy. Nineteen AL patients and 10 healthy controls were enrolled. Diseases were acute myeloid leukemia (17 patients) and acute lymphoblastic leukemia (2 patients). Median WBC, absolute blast count (ABC) and absolute neutrophil count (ANC) at diagnosis were 5280/mm3 (range 840–315100), 162.9/mm3 (range 0–286741) and 796.4/mm3 (range 126–7336), respectively. Mean values of bacreriocidal activity at diagnosis were increased by concentrations of WKYMVm (13.4 at 0 nM; 24.9 at 1 nM; 33.3 at 10 nM; 38.5 at 100 nM; p<0.001), which were also increased in normal samples (20.6 at 0 nM; 41.6 at 1 nM; 51.6 at 10 nM; 66.4 at 100 nM; p<0.001). At each concentrations of WKYMVm, the bacteriocidal activities were inferior to those of normal control (p=0.029, at 0 nM; p=0.015, at 1 nM; p=0.015, at 10 nM; p=0.015, at 100 nM). The bacteriocidal activities were increased (p=0.008, at 0 nM; p=0.015, at 1 nM; p=0.011, at 10 nM; p=0.021, at 100 nM) compared with the corresponding values when patients achieved complete remission (CR). However, bactericidal activities by stimulation of WKYMVm were inferior to normal control even in CR (p=0.036, at 1 nM; p=0.036, at 10 nM; p=0.036, at 100 nM) although base line value were similar (p=1.0, at 0 nM). After hematological recovery of consolidation chemotherapy, the bacteriocidal activities of patients were similar to those of normal control (p=0.533, at 0 nM; p=0.133, at 1 nM; p=0.133, at 10 nM; p=0.133, at 100 nM). In conclusion, the bacteriocidal activities in AL patients were severely decreased at diagnosis and could be enhanced by WKYMVm. Near normal bacteriocidal activities can be achieved when 1 nM or more concentration of WKYMVm is applied in patients with AL. At the end of consolidation, bacteriocidal activities and stimulation by WKYMVm in patients were almost recovered.

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