Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia

Delbuono, Elizabete; Maekawa, Yumi; Latorre, Maria do Rosário Dias de Oliveira; Seber, Adriana; Petrilli, Antônio Sérgio; Braga, Josefina Aparecida Pellegrini; Lee, Maria Lúcia M.

doi:10.1590/s1516-84842008000400010

Cited by 5 publications

(8 citation statements)

References 42 publications

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“…Alternatively, some authors have proposed the detection of Ig/TCR rearrangements by conventional PCR using consensus primers and homo/heteroduplex analysis, despite its lower analytical sensitivity, considering that this approach allows identification of patients with greater residual tumor burden, and then at high risk of relapse. 22 , 27 , 49 , 50 , 78 , 79 , 87 , 88 …”

Section: Discussionmentioning

confidence: 99%

“… 16 , 36 , 38 , 39 , 42 Moreover, accurate and sensitive techniques are technically and economically feasible in places with limited financial resources. 49 , 50 …”

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

“… 5 , 7 , 12 , 24 , 28 , 46 , 55 , 70 The panel could also include other markers of T-lineage cells, such as CD1a, CD2, CD4, CD5, and CD8, and/or aberrant B-lymphoid and myeloid markers, such as CD19, CD13, and CD33, depending on the phenotype determined at diagnosis. 28 , 49 , 70 …”

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

“…MRD levels show a good correlation in PB and BM in T-ALL; however, the correlation is weak in B-ALL, with lower levels of MRD in PB. 49 , 71 …”

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

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Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Rocha¹,

Xavier²,

Souza³

et al. 2016

Mediterr J Hematol Infect Dis

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Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure.The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers.The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL.

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Section: Discussionmentioning

confidence: 99%

“… 16 , 36 , 38 , 39 , 42 Moreover, accurate and sensitive techniques are technically and economically feasible in places with limited financial resources. 49 , 50 …”

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

“…MRD levels show a good correlation in PB and BM in T-ALL; however, the correlation is weak in B-ALL, with lower levels of MRD in PB. 49 , 71 …”

Section: Mrd Evaluation By Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Rocha¹,

Xavier²,

Souza³

et al. 2016

Mediterr J Hematol Infect Dis

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“…However, due to the fact that patients in morphologic remission may present morphologically undetectable amounts of residual leukemic cells, referred as “Minimal Residual Disease” (MRD), different strategies using flow cytometric or molecular techniques have been used to detect these cells in the last decades 5 6 7 . MRD measurement is actually superior to other traditional markers of disease and based in its result, is possible to optimize chemotherapy, minimizing toxicity and decreasing risk of relapse 3 4 5 8 9 .…”

mentioning

confidence: 99%

Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia

Salina

Ferreira

Alves

et al. 2016

Sci Rep

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Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols.

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Identification of potential predictive markers of dexamethasone resistance in childhood acute lymphoblastic leukemia

Dehghan-Nayeri

Rezaei‐Tavirani

Omrani

et al. 2016

J. Cell Commun. Signal.

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Response to dexamethasone (DEXA), as a hallmark drug in the treatment of childhood acute lymphoblastic leukemia (ALL), is one of the pivotal prognostic factors in the prediction of outcome in ALL. Identification of predictive markers of chemoresistance is beneficial to selecting of the best therapeutic protocol with the lowest effect adverse. Hence, we aimed to find drug targets using the 2DE/MS proteomics study of a DEXA-resistant cell line (REH) as a model for poor DEXA responding patients before and after drug treatment. Using the proteomic methods, three differentially expressed proteins were detected, including voltage dependent anion channel 1 (VDAC1), sorting Nexin 3 (SNX3), and prefoldin subunit 6 (PFDN6). We observed low expression of three proteins after DEXA treatment in REH cells. We subsequently verified low expression of resulted proteins at the mRNA level using the quantitative PCR method. These proteins are promising proteins because of their important roles in drug resistance and regulation of apoptosis (VDAC1), protein trafficking (SNX3), and protein folding (PFDN6). Additionally, mRNA expression level of these proteins was assessed in 17 bone marrow samples from children with newly diagnosed ALL and 7 non-cancerous samples as controls. The results indicated that independent of the molecular subtypes of leukemia, mRNA expression of VDAC1, SNX3, and PFDN6 decreased in ALL samples compared with non-cancerous samples particularly in VDAC1 (p < 0.001). Additionally, mRNA expression of three proteins was also declined in high-risk samples compared with standard risk cases. These results demonstrated diagnostic and prognostic value of these proteins in childhood ALL. Furthermore, investigation of protein-protein interaction using STRING database indicated that these proteins involved in the signaling pathway of NR3C1 as dexamethasone target. In conclusion, our proteomic study in DEXA resistant leukemic cells revealed VDAC1, SNX3, and PFDN6 are promising proteins that might serve as potential biomarkers of prognosis and chemotherapy in childhood ALL.

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Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia

Cited by 5 publications

References 42 publications

Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia

Identification of potential predictive markers of dexamethasone resistance in childhood acute lymphoblastic leukemia

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