Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor

Jaime‐Pérez, José Carlos; Pinzón-Uresti, Mónica Andrea; Jiménez-Castillo, Raúl Alberto; Colunga‐Pedraza, Julia E.; González-Llano, Óscar; Gómez‐Almaguer, David

doi:10.1080/10245332.2017.1333294

Cited by 29 publications

(43 citation statements)

References 36 publications

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“…The number of patients with cerebrospinal fluid (CSF) infiltration in this study was detected only in four patients out of 50 cases with available CSF analysis, which is a small number to be statistically analyzed. Splenomegaly, hepatomegaly and lymphadenopathy were clinically detected in 38/49, 38/49 and 36/55 cases, respectively and despite that organ involvement is not included in recent protocols as a risk feature, except for the central nervous system and testis, but some studies observed that it can still decrease remission and increase relapse rates [24].…”

Section: Discussionmentioning

confidence: 99%

Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group

Alrayes¹,

Hammad²,

Baddiny³

et al. 2019

JCT

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Angiogenesis has an important role in pathophysiology of cancer. FMS-like tyrosine kinase 3 (FLT3) is implicated in hematopoietic malignancies. Their role in childhood acute lymphoblastic leukemia (ALL) pathogenesis needs more enlightenment. Expression of vascular endothelial growth factor receptor-1 and-2 (VEGFR-1 and-2), as well as FLT3 were assessed by flow cytometry in bone marrow (BM) blasts of 55 newly diagnosed children with ALL. Patients included B cell ALL (B-ALL) group (n = 41) and T cell ALL (T-ALL) group (n = 14). Comparison between groups revealed a significant increase in blasts percent (%) expressing FLT3 and FLT3 intensity detected in BALL group (p = 0.004 and p = 0.02, respectively). In BALL patients, a significant positive correlation was seen between blasts % expressing FLT3 and blasts percentage infiltrating BM (r = 0.405; p = 0.009), also positive correlation was seen between % of blasts expressing VEGFR-1 and VEGFR-2 (r = 0.704; p < 0.001). In TALL group, blast % expressing FLT3 revealed significant positive correlations with blast % expressing VEGFR-1, and those expressing VEGFR-2 (r = 0.627; p = 0.016, and r = 0.654; p = 0.011, respectively). In addition, significant correlation was seen in blasts % expressing all; FLT3, VEGFR-1 and-2, with blasts % expressing stem cell marker CD34 (r = 0.826; p = 0.001, r = 0.596; p = 0.041, and r = 0.798; p = 0.002, respectively). Conclusion: Expression of VEGFR-1, VEGFR-2 and FLT3 were demonstrated and linked on leukemic blasts of ALL which highlights their role in pathogenesis. FLT3 expression plays a role in facilitating blasts proliferation in BM in BALL. FLT3, VEGFR-1 and-2 could be used in future profiling of CD34 + leukemic stem cell pool in TALL .

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Section: Discussionmentioning

confidence: 99%

Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group

Alrayes¹,

Hammad²,

Baddiny³

et al. 2019

JCT

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“…With the development of contemporary treatment regimens and advances in epigenomic and genomic profiling, the overall survival (OS) in pediatric patients with ALL is >80%, and our understanding of the biology of ALL relapse has remarkably improved and facilitated more precise risk determination during the past 10 years (2,3). However, 20-35% of patients with ALL experience relapse, and treating relapsed ALL patients is challenging (4)(5)(6). ALL commonly arises from a series of genetic alterations, which may occur due to inherited susceptibility, exogenous or endogenous exposure to various mutagens or, rarely, by chance (7,8).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of the tumor suppressor protein p53 gene in childhood acute lymphoblastic leukemia

et al. 2019

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The tumor suppressor protein p53 (TP53) gene is associated with various types of cancer; however, little is known about TP53 expression in patients with childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the prognostic value of TP53 expression in childhood ALL. To achieve this, TP53 mRNA levels of 146 children with ALL and 23 child donors with idiopathic thrombocytopenic purpura were determined by reverse transcription-quantitative PCR. Relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The results demonstrated that TP53 mRNA level in patients with ALL was higher compared with that in the ITP donors (P=0.019). Patients with highly-expressed TP53 exhibited lower percentages of peripheral blood blast, higher platelet counts and inferior complete remission rates compared with patients with low expression of TP53. Survival analyses revealed that high TP53 expression was associated with poor OS and RFS in childhood ALL (P=0.018 and P=0.028, respectively) and was an independent prognostic factor in multivariate analysis for poor RFS (P<0.001) and OS (P<0.001). In conclusion, high TP53 expression is associated with poor outcomes and may be used as a molecular prognostic marker to be incorporated into an improved risk classification system for childhood ALL.

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“…The molecular pathogenesis of ALL involves the aberrant expression of protooncogenes in several signaling pathways, chromosomal translocations of transcription factors and hyperdiploidy (1). Currently, ~80% of all newly diagnosed pediatric patients with ALL can become disease-free following adequate treatment; however, a small number of children still experience ALL relapse (2). Treatment of relapsed ALL is largely ineffective, as the response rate to chemotherapeutic drugs is only 10-20%, which is often attributed to the effect of ATP-binding cassette (ABC) transporter family members, multidrug resistance 1 (MDR1) and MDR-associated protein (MRP) (3,4).…”

Section: Introductionmentioning

confidence: 99%

Wnt/β‑catenin inhibition reverses multidrug resistance in pediatric acute lymphoblastic leukemia

Zhuang

et al. 2018

Oncol Rep

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Although ~80% of newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL) become disease-free following appropriate treatment, relapses frequently occur, with dismal prognosis. Therefore, it is urgent to develop novel therapeutic modalities. Resistance to chemotherapy is a major obstacle for the treatment of relapsed ALL. It has been indicated that Wnt pathway is potentially associated with leukemia recurrence. In the current study, a vincristine (VCR)-resistant variant of the human ALL cell line BALL-1 (BALL-1/VCR) that also had relatively specific resistance to both doxorubicin and etoposide was generated. Over-activation of the Wnt/β-catenin signaling pathway was observed in BALL-1/VCR cells, whereas Dickkopf-related protein 1 selectively suppressed the Wnt signaling pathway and sensitized the response of BALL-1/VCR to anticancer agents. In addition, prednisolone exposure in combination with Wnt inhibition restored chemo-sensitivity in relapsed ALL blasts. Since the resistance of BALL-1/VCR cells is potentially attributed to the overexpression of MDR-associated protein 1 (MRP1), the development of drug resistance in relapsed ALL may associated with the overexpression of MRP1 and P-glycoprotein. The results of this study demonstrated that, as a potential candidate to mimic relapsed ALL, BALL-1/VCR could be used in further research, while Wnt-inhibition may become a promising therapeutic approach for treating ALL.

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Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor

Abstract: A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.

Cited by 29 publications

References 36 publications

Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group

Angiogenic and FLT3 Receptors Expression in Acute Lymphoblastic Leukemia in Pediatric Age Group

Prognostic significance of the tumor suppressor protein p53 gene in childhood acute lymphoblastic leukemia

Wnt/β‑catenin inhibition reverses multidrug resistance in pediatric acute lymphoblastic leukemia

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