Overall Survival of Adult Acute Lymphoblastic Leukemia (ALL) Patients By Facility Volume and Type: A National Cancer Database Report

Dykes, Kaitlyn; Chou, Jiling; Taylor, Allison; Ma, Xiaonan; Lai, Catherine

doi:10.1182/blood-2022-156291

Cited by 1 publication

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“…1,2 In contrast to the successful history of childhood leukemia treatment, with the survival rates around 90%, the treatment of adult ALL has only shown modest improvements over the last 2 decades, with the overall survival rates varying from 15% to 40%. 3,4 The normal hematopoietic process involves several signaling pathways that ensure normal cell survival. The phosphoinositide 3-kinase (PI3K)/Akt and mitogen activated protein kinase (MAPK) signaling pathways stimulate mitosis, leading cells to proliferation and are also involved in inhibition of apoptosis, being both crucial in normal cell growth.…”

Section: Discussionmentioning

confidence: 99%

“…Acute lymphoblastic leukemias (ALL) are clonal diseases caused by sequential acquisition of genetic alterations (mutations) in immature progenitors, resulting in differentiation disturbance leading to proliferation of immature lymphoid blast cells 1,2 . In contrast to the successful history of childhood leukemia treatment, with the survival rates around 90%, the treatment of adult ALL has only shown modest improvements over the last 2 decades, with the overall survival rates varying from 15% to 40% 3,4 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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