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

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 leuke...

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Published in:Cancer reports 2023-12, Vol.6 (12), p.e1912-n/a
Main Authors: Loureiro, Gustavo, Bahia, Daniella M., Lee, Maria Lucia M., Souza, Mair Pedro, Kimura, Eliza Y. S., Rezende, Denise Carvalho, Silva, Marçal Cavalcante de Andrade, Chauffaille, Maria de Lourdes L. F., Yamamoto, Mihoko
Format: Article
Language:English
Subjects:
Adolescent
ALL
Apoptosis
Bone marrow
Cell growth
ERK
Flow cytometry
Glycoproteins
Humans
Investigations
Kinases
Leukemia
MAPK
Medical prognosis
Mitogen-Activated Protein Kinases - metabolism
Original
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
PI3K/Akt
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - physiology
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container_title Cancer reports
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creator Loureiro, Gustavo
Bahia, Daniella M.
Lee, Maria Lucia M.
Souza, Mair Pedro
Kimura, Eliza Y. S.
Rezende, Denise Carvalho
Silva, Marçal Cavalcante de Andrade
Chauffaille, Maria de Lourdes L. F.
Yamamoto, Mihoko
description 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). Methods We 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. Results Ten 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 
doi_str_mv 10.1002/cnr2.1912
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S. ; Rezende, Denise Carvalho ; Silva, Marçal Cavalcante de Andrade ; Chauffaille, Maria de Lourdes L. F. ; Yamamoto, Mihoko</creator><creatorcontrib>Loureiro, Gustavo ; Bahia, Daniella M. ; Lee, Maria Lucia M. ; Souza, Mair Pedro ; Kimura, Eliza Y. S. ; Rezende, Denise Carvalho ; Silva, Marçal Cavalcante de Andrade ; Chauffaille, Maria de Lourdes L. F. ; Yamamoto, Mihoko</creatorcontrib><description>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). Methods We 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. Results Ten 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 &lt; .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). Conclusion Our 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.</description><identifier>ISSN: 2573-8348</identifier><identifier>EISSN: 2573-8348</identifier><identifier>DOI: 10.1002/cnr2.1912</identifier><identifier>PMID: 37867416</identifier><language>eng</language><publisher>United States: John Wiley &amp; Sons, Inc</publisher><subject>Adolescent ; ALL ; Apoptosis ; Bone marrow ; Cell growth ; ERK ; Flow cytometry ; Glycoproteins ; Humans ; Investigations ; Kinases ; Leukemia ; MAPK ; Medical prognosis ; Mitogen-Activated Protein Kinases - metabolism ; Original ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; PI3K/Akt ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction - physiology</subject><ispartof>Cancer reports, 2023-12, Vol.6 (12), p.e1912-n/a</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC.</rights><rights>2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.</rights><rights>2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c5372-d348df0ddd23eade3c27443dad47a7692af8bc25141de262a73c67d117e3f3e23</cites><orcidid>0000-0002-1525-2273</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10728523/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3090227718?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11561,25752,27923,27924,37011,37012,44589,46051,46475,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37867416$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Loureiro, Gustavo</creatorcontrib><creatorcontrib>Bahia, Daniella M.</creatorcontrib><creatorcontrib>Lee, Maria Lucia M.</creatorcontrib><creatorcontrib>Souza, Mair Pedro</creatorcontrib><creatorcontrib>Kimura, Eliza Y. S.</creatorcontrib><creatorcontrib>Rezende, Denise Carvalho</creatorcontrib><creatorcontrib>Silva, Marçal Cavalcante de Andrade</creatorcontrib><creatorcontrib>Chauffaille, Maria de Lourdes L. F.</creatorcontrib><creatorcontrib>Yamamoto, Mihoko</creatorcontrib><title>MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia</title><title>Cancer reports</title><addtitle>Cancer Rep (Hoboken)</addtitle><description>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). Methods We 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. Results Ten 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 &lt; .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). Conclusion Our 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.</description><subject>Adolescent</subject><subject>ALL</subject><subject>Apoptosis</subject><subject>Bone marrow</subject><subject>Cell growth</subject><subject>ERK</subject><subject>Flow cytometry</subject><subject>Glycoproteins</subject><subject>Humans</subject><subject>Investigations</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>MAPK</subject><subject>Medical prognosis</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Original</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>PI3K/Akt</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction - physiology</subject><issn>2573-8348</issn><issn>2573-8348</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kk9v2yAchq1p01p1PewLTEi7bIc0_IvBpymKujVKt1VVd0a_AE5IsUnBbpVvP5y0VTtpJxA8PHqBtyg-EnxGMKZj3UZ6RipC3xTHdCLYSDIu376YHxWnKW0wxkSWjFbsfXHEhCwFJ-VxcftzerUYn18vELQGXc3ZYjxd3KDkVi14167QFrr1A-wSgmgR6M7dQ2cNci0CE7xN2rbd_iyY3ueZ7juL_K7ZrsPSQ-qcRt72t7Zx8KF4V4NP9vRxPCn-fD-_mV2MLn__mM-mlyM9YYKOTM5samyMocyCsUxTwTkzYLgAUVYUarnUdEI4MZaWFATTpTCECMtqZik7KeYHrwmwUdvoGog7FcCp_UKIKwUxB_NWaYOl5lBWwmhe42oQS8Lqsq4Fr_Ayu74dXNt-2Vgz3DaCfyV9vdO6tVqFe0WwoHJCWTZ8eTTEcNfb1KnG5VfzHlob-qSolFhSIvmAfv4H3YQ-5o9IiuEKUyoEkZn6eqB0DClFWz-nIVgNlVBDJdRQicx-ehn_mXwqQAbGB-DBebv7v0nNfl3TvfIvMlO_2Q</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Loureiro, Gustavo</creator><creator>Bahia, Daniella M.</creator><creator>Lee, Maria Lucia M.</creator><creator>Souza, Mair Pedro</creator><creator>Kimura, Eliza Y. S.</creator><creator>Rezende, Denise Carvalho</creator><creator>Silva, Marçal Cavalcante de Andrade</creator><creator>Chauffaille, Maria de Lourdes L. F.</creator><creator>Yamamoto, Mihoko</creator><general>John Wiley &amp; Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1525-2273</orcidid></search><sort><creationdate>202312</creationdate><title>MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia</title><author>Loureiro, Gustavo ; Bahia, Daniella M. ; Lee, Maria Lucia M. ; Souza, Mair Pedro ; Kimura, Eliza Y. 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S.</au><au>Rezende, Denise Carvalho</au><au>Silva, Marçal Cavalcante de Andrade</au><au>Chauffaille, Maria de Lourdes L. F.</au><au>Yamamoto, Mihoko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia</atitle><jtitle>Cancer reports</jtitle><addtitle>Cancer Rep (Hoboken)</addtitle><date>2023-12</date><risdate>2023</risdate><volume>6</volume><issue>12</issue><spage>e1912</spage><epage>n/a</epage><pages>e1912-n/a</pages><issn>2573-8348</issn><eissn>2573-8348</eissn><abstract>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). Methods We 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. Results Ten 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 &lt; .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). Conclusion Our 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.</abstract><cop>United States</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>37867416</pmid><doi>10.1002/cnr2.1912</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1525-2273</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adolescent
ALL
Apoptosis
Bone marrow
Cell growth
ERK
Flow cytometry
Glycoproteins
Humans
Investigations
Kinases
Leukemia
MAPK
Medical prognosis
Mitogen-Activated Protein Kinases - metabolism
Original
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
PI3K/Akt
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - physiology
title MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia
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