Lncrna Famlf-2 Inhibits Acute Lymphoblastic Leukemia Apoptosis through the p38 MAPK Signaling Pathway

Lai, Xiaolin; Shi, Shuiling; Huang, Yuanmao; Cai, Yuanhua; Chen, Zhixiang; Wang, Xuechun; Tu, Fuquan; Pan, Lili; Li, Xiaofan; Ye, Luya; Li, Yang; Wang, Shaoyuan

doi:10.1182/blood-2022-165091

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“…20,21 Importantly, components of these pathways have emerged as promising targets for the development of specific inhibitory compounds. 22,23 Drugs, such as perifosine, 24 andrographolide, 25 and PKI-587, 26 have shown anti-leukemic effects through PI3K/Akt pathway blockade. In addition, drug sensitivity to the mitogen-activated protein kinase (MEK) inhibitors has been shown to correlate with ERK activation status in AML.…”

Section: Discussionmentioning

confidence: 99%

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MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia

Loureiro,

Bahia,

Lee

et al. 2023

Cancer Reports

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Background: The mitogen‐activated protein kinase (MAPK)/ERK signaling cascade and the phosphoinosytol‐3 phosphate/Akt (PI3K/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated.Aims: To assess the activity and prognostic implications of MAPK/ERK and PI3K/Akt pathways in adult (ALL).MethodsWe examined 28 precursor‐B‐cell ALL and 6 T‐cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt.ResultsTen out of 15 (67%) ALL fresh samples (7 B‐cell, 3 T‐cell) showed constitutive p‐ERK expression. The p‐ERK mean fluorescent index ratio (MFI (R)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74–3.10] vs. 1.08 [1.02–1.21], respectively [p = .069]) and was significantly lower than in leukemic cell lines (median MFI (R) 3.83 [3.71–5.97] [p < .001]). Expression of p‐Akt was found in 35% (12/34) (10 B‐cell, 2 T‐cell). The median MFI (R) expression for p‐Akt in primary blast cell was 1.13 (0.48–9.90) compared to 1.01 (1.00–1.20) in normal T lymphocytes (p = ns) and lower than in leukemic cell lines (median MFI (R) 2.10 [1.77–3.40] [p = .037]). Moreover, expression of p‐ERK was negatively associated with the expression of CD34 (1.22 [0.74–1.33] vs. 1.52 [1.15–3.10] for CD34(+) and CD34(−) group, respectively, p = .009).ConclusionOur findings suggest that both MAPK/ERK and PI3K/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.

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Section: Discussionmentioning

confidence: 99%

“…Importantly, components of these pathways have emerged as promising targets for the development of specific inhibitory compounds 22,23 . Drugs, such as perifosine, 24 andrographolide, 25 and PKI‐587, 26 have shown anti‐leukemic effects through PI3K/Akt pathway blockade.…”

Section: Introductionmentioning

confidence: 99%