Positive Expression of MUC1 Gene Is a Poor Prognostic Factor in Acute Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4294-4294
Author(s):  
Ren-wei Huang ◽  
Guo-wei Li ◽  
Dong-ning Wang ◽  
Xu-dong Li ◽  
Gui-zhen Lin ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Acute Leukemia ◽  
Residual Disease ◽  
Myelogenous Leukemia ◽  
Muc1 Expression ◽  
Poor Prognostic Factor ◽  
Positive Expression ◽  
Muc1 Gene ◽  
Pcr Products ◽  
Expression Rate

Abstract Objective: To study the expression of MUC1 in acute leukemia and its clinical significance. Methods: Expression of MUC1 mRNA was detected in 73 newly diagnosed and relapsed patients of acute leukemia by reverse transcriptase polymerase reaction(RT-PCR). The MUC1 positive PCR products were analyzed by digestion with pst I. With clinical observation, the relationship of expression of MUC1 gene and treatment results were done. Results: The expression of MUC1 was positive in 36 of 73 AL patients (49.3%). The MUC1 expression rate was 39.1% in ALL and 52.2% in AML and they show no significance difference. MUC1 gene was undetectable in 23 healthy subjects. Nineteen of 21 (90.5%) MUC1-negative non-M3 acute leukemia patients got CR while 14 of 22 (63.6%) MUC1-positive non-M3 acute leukemia patients got CR which showed significance difference (p<0.05); Only 9 of 16 cases of MUC1-positive non-M3 AML patients got CR(56.3%), while 10 of 11 patients of MUC1-negative non-M3 AML got CR(90.9%). The expression of MUC1 could turn negative after CR. There was no mutation of MUC1 gene correlating with digested site of pst I. Conclusion: MUC1 expression is observed in some acute leukemia patients. The positive expression of MUC1 is not different between AML and ALL. The AML patients whose MUC1 gene showed positive got lower CR rate. It indicates that the expression of MUC1 can be used as a poor prognostic factor in AML and a marker for detection of minimal residual disease in AL.

scholarly journals WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3071-3079 ◽  
Author(s):  
K Inoue ◽  
H Sugiyama ◽  
H Ogawa ◽  
M Nakagawa ◽  
T Yamagami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prognostic Factor ◽  
Acute Leukemia ◽  
Dna Markers ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Wt1 Gene ◽  
Rt Pcr ◽  
Minimal Residual

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non- Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(- 4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.

scholarly journals WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3071-3079 ◽  
Author(s):  
K Inoue ◽  
H Sugiyama ◽  
H Ogawa ◽  
M Nakagawa ◽  
T Yamagami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prognostic Factor ◽  
Acute Leukemia ◽  
Dna Markers ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Wt1 Gene ◽  
Rt Pcr ◽  
Minimal Residual

Abstract The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non- Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(- 4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.

scholarly journals The myth of the second remission of acute leukemia in the adult

Blood ◽  
2013 ◽  
Vol 121 (7) ◽  
pp. 1077-1082 ◽  
Author(s):  
Stephen J. Forman ◽  
Jacob M. Rowe
Keyword(s):  
Acute Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Myelogenous Leukemia ◽  
Curative Therapy ◽  
Successful Transplantation ◽  
Acute Myelogenous ◽  
First Remission ◽  
First Relapse

Abstract Although the majority of adult patients with both acute lymphoblastic leukemia and acute myelogenous leukemia achieve remission with upfront chemotherapy, many patients still suffer relapse. Often, the strategy is proposed of treating patients with relapsed leukemia into a second remission (CR2) and then proceeding to allogeneic transplantation as the definitive curative approach. However, the long-term outcomes of such a strategy are poor: the 5-year overall survival from first relapse for patients with acute leukemia is only approximately 10%. This Perspective highlights the fact that most patients do not achieve CR2 and therefore never really have an opportunity for a potential curative therapy. Although patients who undergo transplantation after relapse may be cured, those who do not achieve CR2 are rarely candidates for transplantation; therefore, the overall outcome for patients who relapse is dismal. There is therefore an urgent need not only for more effective upfront therapy to prevent relapse, but also for the development of therapies that can serve as effective bridging treatments between relapse and transplantation. We suggest that more optimal use of minimal residual disease detection during first remission may also improve the chances for successful transplantation therapy via earlier reinduction therapy, allowing transplantation before overt relapse.

Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3794-3800 ◽  
Author(s):  
Jorge E. Cortes ◽  
Moshe Talpaz ◽  
Francis Giles ◽  
Susan O'Brien ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Imatinib Mesylate ◽  
Multivariate Analyses ◽  
Clonal Evolution ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Poor Prognostic Factor ◽  
Prognostic Relevance ◽  
Independent Poor Prognostic Factor ◽  
Response Versus

Abstract Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome–positive chronic myelogenous leukemia (Ph-positive CML). However, its prognostic relevance in the era of imatinib therapy is unknown. We investigated the independent prognostic relevance of CE in 498 patients with Ph-positive CML treated with imatinib for chronic or accelerated phases. One hundred twenty-one patients had CE alone (n = 70) or with other accelerated phase criteria (n = 51). Patients were compared in 4 categories: chronic phase (n = 295), CE only (n = 70), accelerated phase without CE (n = 82), and accelerated phase with CE (n = 51). Statistical methods used established methodologies for univariate and multivariate analyses. In chronic and accelerated phases of CML, CE was not associated with significant differences in major or complete cytogenetic response rates, but it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P = .005) and accelerated phase (P = .03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is an independent poor prognostic factor for survival in both chronic and accelerated phases of CML. The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy.

METHODS OF MULTICLASSICATION OF BONE MARROW CELLS FOR THE DIAGNOSIS OF ACUTE LEUKEMIA AND MINIMAL RESIDUAL DISEASE (ON THE MATERIALS OF THE LABORATORY OF HEMATOPOIESIS OF N. N. BLOKHIN NATIONAL MEDICAL RESEARCH CENTER OF ONCOLOGY)

2020 ◽  
pp. 155-158
Author(s):  
Валентина Викторовна Дмитриева ◽  
Николай Николаевич Тупицын ◽  
Евгений Валерьевич Поляков ◽  
Софья Сергеевна Денисюк
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Medical Research ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Binary Classification ◽  
National Medical ◽  
Cell Class ◽  
Minimal Residual ◽  
Marrow Cells

Применение методов и средств цифровой обработки изображений при распознавании типов клеток крови и костного мозга для повышения качества диагностики острых лейкозов является актуальной научно-технической задачей, отвечающей стратегии развития технологий искусственного интеллекта в медицине. В работе предложен подход к мультиклассификации клеток костного мозга при диагностике острых лейкозов и минимальной остаточной болезни. Для проведения экспериментальных исследований сформирована выборка из 3284 изображений клеток, представленных Лабораторией гемопоэза Национального медицинского исследовательского центра онкологии им. Н.Н. Блохина. Предложенный подход к мультиклассификации клеток костного мозга основан на бинарной модели классификации для каждого из исследуемых классов относительно остальных. В рассматриваемой работе бинарная классификация выполняется методом опорных векторов. Метод мультиклассификации был программно реализован с применением интерпретатора Python 3.6.9. Входными данными программы служат файлы формата *.csv с таблицами морфологических, цветовых, текстурных признаков для каждой из клеток используемой выборки. В выборке представлено девять типов клеток костного мозга. Выходными данными программы мультиклассификации являются значения точности классификации на тестовой выборке, которые отражают совпадение прогнозируемого класса клетки с фактическим (верифицированным) классом клетки. “Эксперимент показал следующие результаты: точность мультиклассификации рассматриваемых типов клеток в среднем составила: 87% на тестовом наборе, 88% на обучающем наборе данных. Проведенное исследование является предварительным. В дальнейшем планируется увеличить число классов клеток, объем выборок различных типов клеток и с уточнением результатов мультиклассификации The use of methods and means of digital image processing in the recognition of types of blood cells and bone marrow to improve the quality of diagnosis of acute leukemia is an urgent scientific and technical task that meets the strategy for the development of artificial intelligence technologies in medicine. The paper proposes an approach to the multiclassification of bone marrow cells in the diagnosis of acute leukemia and minimal residual disease. For experimental studies, a sample of 3284 images of cells was formed, submitted by the Hematopoiesis Laboratory of the National Medical Research Center of Oncology named after V.I. N.N. Blokhin. The proposed approach to the multiclassification of bone marrow cells is based on a binary classification model for each of the studied classes relative to the others. In the work under consideration, binary classification is performed by the support vector machine. The multiclassification method was implemented programmatically using the Python 3.6.9 interpreter. The input data of the program are * .csv files with tables of morphological, color, texture features for each of the cells of the sample used. The sample contains nine types of bone marrow cells. The output data of the multiclassification program are the classification accuracy values on the test sample, which reflect the coincidence of the predicted cell class with the actual (verified) cell class. “The experiment showed the following results: the accuracy of multiclassification of the considered types of cells on average was: 87% on the test set, 88% on the training data set. This study is preliminary. In the future, it is planned to increase the number of classes of cells, the volume of samples of various types of cells and with the refinement of the results of multiclassification

scholarly journals Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1796
Author(s):  
Markus Eckstein ◽  
Verena Lieb ◽  
Rudolf Jung ◽  
Danijel Sikic ◽  
Katrin Weigelt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Potential Candidate ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Muscle Invasive ◽  
Disease Specific

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

scholarly journals BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 924
Author(s):  
Elena Zerkalenkova ◽  
Svetlana Lebedeva ◽  
Aleksandra Borkovskaia ◽  
Olga Soldatkina ◽  
Olga Plekhanova ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Residual Disease ◽  
Chromosomal Rearrangements ◽  
Strong Impact ◽  
Acute Leukemias ◽  
Dna And Rna ◽  
Targeted Ngs ◽  
Childhood Acute Leukemia ◽  
Next Generation Sequencing Ngs ◽  
The Given

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients’ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subsequent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients.

scholarly journals 1153. Characterization of Invasive Mold Infections in Acute Leukemia and Hematopoietic Stem Cell Transplant Recipient Patients and Risk Factors for Mortality - a Single Center Experience

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S603-S604
Author(s):  
Ryan Kubat ◽  
Praveen Subramanian ◽  
Yanming Li ◽  
Kassem Hammoud ◽  
Albert Eid ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Acute Leukemia ◽  
Regression Model ◽  
Hematopoietic Stem Cell ◽  
Cox Model ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Invasive Mold Infections

Abstract Background Invasive mold infections (IMIs) remain a significant cause of morbidity and mortality in patients with acute leukemia (AL) and those undergoing hematopoietic stem cell transplantation (HSCT). We describe the epidemiology of IMIs, the incidence of IMI in patients with acute myelogenous Leukemia (AML) post HSCT, and risk factors for mortality. Methods Patients were identified using ICD9 and ICD10 codes using a University of Kansas internal database from 2009-2019, microbiology records, and an AML HSCT database and were followed through May 1st, 2020. Patients’ electronic medical records were reviewed for inclusion. IMI was defined as proven or probable using the 2009 National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) guidelines. Incidence was calculated as IMI cases/100-person-years. Risk factors for overall mortality were evaluated using a Cox regression model. Results We included 138 patients: 79 developed IMI after HSCT (8 autologous, 71 allogeneic) and 59 developed IMI after AL diagnosis. Seventeen of the AL patients underwent HSCT after IMI diagnosis (12 within 100 days of IMI). Proven IMI occurred in 45 (32.6%) and probable IMI occurred in 93 (67.4%) patients. The most common prophylactic agent prior to IMI diagnosis was fluconazole (31.2%), with 21.0% receiving none. Aspergillus was the most commonly identified mold with 91 (65.9%) cases. The average treatment duration was 101 (range 0 - 799) days. The incidence of IMI in patients with AML who underwent HSCT was 2.35 cases/100 person-years. All-cause mortality among patients with AL or HSCT who developed IMI was 23.1% at 6 weeks, 34.1% at 12 weeks, and 61.2% at 1 year. On univariate Cox model, Karnofsky performance status &gt; 70 was associated with lower mortality (hazard ratio (HR) 0.317, 95% confidence interval (CI) [0.110, 0.914]) among HSCT recipients. ICU admission within 7 days prior to IMI diagnosis (HR 6.469, 95% CI [1.779, 23.530]) and each one point increase in BMI (HR 1.051, CI [1.001, 1.103]) were associated with increased mortality in the AL group. Figure 1 - Invasive mold infections by pathogen in HSCT-recipients and acute leukemia patients from 2009-2019. Figure 2 - Antifungal prophylactic agents prescribed for at least one week at time of IMI diagnosis Table 1 - Univariate survival analysis calculated using a Cox proportional-hazards regression model among patients who developed IMI after HSCT and patients who developed IMI after acute leukemia diagnosis Conclusion IMIs are associated with significant mortality in HSCT recipients and AL patients; patients at higher risk for mortality include those with lower baseline Karnofsky scores, recent ICU admissions, and higher BMI at time of IMI diagnosis. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

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