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墨西哥瓦哈卡州儿童急性白血病中预后不良的生物分子因素非常常见。

Poor Prognosis Biomolecular Factors Are Highly Frequent in Childhood Acute Leukemias From Oaxaca, Mexico.

机构信息

Laboratorio Juárez, Medicina de Laboratorio Clínico de Alta Especialidad, Biología Molecular e Investigación Clínica, Oaxaca de Juárez, Oaxaca, México.

Servicio de Hematología, Hospital de la Niñez Oaxaqueña "Doctor Guillermo Zárate Mijangos", Secretaría de Salud, Oaxaca de Juárez, Oaxaca, México.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820928436. doi: 10.1177/1533033820928436.

Abstract

OBJECTIVE

To investigate the cellular and molecular epidemiology of acute leukemias in vulnerable populations of children and adolescents in Oaxaca de Juarez, Mexico.

MATERIAL AND METHODS

Descriptive, cross-sectional and retrospective study, conducted from 2014 to 2018 in which profiles of molecular and immunophenotypic aberrations were investigated in children and adolescents diagnosed with acute leukemia, by evaluating 28 molecular abnormalities by HemaVision-Q28 multiplex RT-PCR kit and standardized EuroFlow Immunophenotyping of bone marrow cells.

RESULTS

We included 218 patients, with 82.5% younger than 14 years and 17.5% adolescents. The median age was 9 years and a main peak of incidence was recorded at age of 4 to 5 years. B-cell acute lymphoblastic leukemia was diagnosed in 70.64% of all cases, acute myeloid leukemia was in 22.48%, T-cell acute lymphoblastic leukemia in 6.42%, and mixed lineage acute leukemia in 0.46% of cases. Overall, chromosomal translocations were positive in 29.82% of cases. While 65.31% of patients with acute myeloid leukemia reported aberrancies, only in 18.83% of B-cell acute lymphoblastic leukemia cases genetic abnormalities were obvious. Surprisingly, most prevalent translocations in B-cell acute lymphoblastic leukemia were t(9;22) in 20.7%, followed by t(4;11) in 17.2% and t(6;11) in 13.8%, whereas patients with acute myeloid leukemia showed t(15;17) in 40.6% and t(8;21) in 21.9%. In contrast, an homogeneous expression of t(3;21) and t(6;11) was recorded for T-cell acute lymphoblastic leukemia and mixed lineage acute leukemia cases, respectively. Except for t(1;19), expressed only by pre-B cells, there was no association of any of the studied translocations with differentiation stages of the B-leukemic developmental pathway.

CONCLUSION

Our findings identify near 50% of patients with acute lymphoblastic leukemia at debut with high-risk translocations and poor prognosis in B-cell acute lymphoblastic leukemia as well as an unexpected increase of acute myeloid leukemia cases in young children, suggesting a molecular shift that support a higher incidence of poor prognosis cases in Oaxaca.

摘要

目的

研究墨西哥瓦哈卡州奥萨卡市儿童和青少年弱势群体中急性白血病的细胞和分子流行病学。

材料和方法

这是一项描述性、横断面和回顾性研究,于 2014 年至 2018 年进行,通过评估 28 种分子异常,对诊断为急性白血病的儿童和青少年的分子和免疫表型异常进行了研究,使用 HemaVision-Q28 多重 RT-PCR 试剂盒和骨髓细胞标准化 EuroFlow 免疫表型分析。

结果

共纳入 218 例患者,82.5%年龄小于 14 岁,17.5%为青少年。中位年龄为 9 岁,发病高峰年龄为 4-5 岁。所有病例中 B 细胞急性淋巴细胞白血病诊断占 70.64%,急性髓系白血病占 22.48%,T 细胞急性淋巴细胞白血病占 6.42%,混合谱系急性白血病占 0.46%。总体而言,染色体易位阳性率为 29.82%。虽然 65.31%的急性髓系白血病患者存在异常,但在 18.83%的 B 细胞急性淋巴细胞白血病病例中明显存在遗传异常。令人惊讶的是,B 细胞急性淋巴细胞白血病中最常见的易位是 t(9;22)占 20.7%,其次是 t(4;11)占 17.2%,t(6;11)占 13.8%,而急性髓系白血病患者中 t(15;17)占 40.6%,t(8;21)占 21.9%。相比之下,T 细胞急性淋巴细胞白血病和混合谱系急性白血病病例分别表现出 t(3;21)和 t(6;11)的同质表达。除了仅在前 B 细胞中表达的 t(1;19)外,研究的任何易位均与 B 细胞白血病发育途径的分化阶段无关。

结论

我们的研究结果发现,近 50%的急性淋巴细胞白血病患者在发病时存在高危易位和预后不良的 B 细胞急性淋巴细胞白血病,以及儿童中急性髓系白血病病例的意外增加,这表明存在分子变化,支持在瓦哈卡州发生更多预后不良病例的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06af/7340349/b0d1d0896b99/10.1177_1533033820928436-fig5.jpg

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