Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia

Lisa Russell, Melania Capasso, Inga Vater, Takashui Akasaka, Olivier Bernard, Maria Jose Calasanz, Thiruppavaii Chandrasekaran, Elise Chapiro, Stephen Gesk, Mike Griffiths, David Guttery, Claudia Haferlach, Lana Harder, Olaf Heidenreich, Julie Irving, Lyndal Kearney, Florence Nguyen-Khac, Lee Machado, Lynne Minto, Aneela MajidAnthony Moorman, Heather Morrison, Vikki Rand, Jonathan Strefford, Claire Schwab, Holger Tonnies, Martin Dyer, Reiner Siebert, Christine Harrison

Research output: Contribution to journalArticle

Abstract

We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations
Original languageEnglish
Pages (from-to)2688-2698
Number of pages10
JournalBlood
Volume114
Issue number13
DOIs
Publication statusPublished - 29 Jul 2009

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Cytokine Receptors
B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genes
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Cell Line
Mutation
Sex Chromosomes
Down Syndrome
Chromosome Aberrations
Incidence

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Russell, L., Capasso, M., Vater, I., Akasaka, T., Bernard, O., Calasanz, M. J., ... Harrison, C. (2009). Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood, 114(13), 2688-2698. https://doi.org/10.1182/blood-2009-03-208397
Russell, Lisa ; Capasso, Melania ; Vater, Inga ; Akasaka, Takashui ; Bernard, Olivier ; Calasanz, Maria Jose ; Chandrasekaran, Thiruppavaii ; Chapiro, Elise ; Gesk, Stephen ; Griffiths, Mike ; Guttery, David ; Haferlach, Claudia ; Harder, Lana ; Heidenreich, Olaf ; Irving, Julie ; Kearney, Lyndal ; Nguyen-Khac, Florence ; Machado, Lee ; Minto, Lynne ; Majid, Aneela ; Moorman, Anthony ; Morrison, Heather ; Rand, Vikki ; Strefford, Jonathan ; Schwab, Claire ; Tonnies, Holger ; Dyer, Martin ; Siebert, Reiner ; Harrison, Christine. / Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. In: Blood. 2009 ; Vol. 114, No. 13. pp. 2688-2698.
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title = "Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia",
abstract = "We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5{\%} in childhood ALL (0.8{\%} with the translocation, 4.2{\%} with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations",
author = "Lisa Russell and Melania Capasso and Inga Vater and Takashui Akasaka and Olivier Bernard and Calasanz, {Maria Jose} and Thiruppavaii Chandrasekaran and Elise Chapiro and Stephen Gesk and Mike Griffiths and David Guttery and Claudia Haferlach and Lana Harder and Olaf Heidenreich and Julie Irving and Lyndal Kearney and Florence Nguyen-Khac and Lee Machado and Lynne Minto and Aneela Majid and Anthony Moorman and Heather Morrison and Vikki Rand and Jonathan Strefford and Claire Schwab and Holger Tonnies and Martin Dyer and Reiner Siebert and Christine Harrison",
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Russell, L, Capasso, M, Vater, I, Akasaka, T, Bernard, O, Calasanz, MJ, Chandrasekaran, T, Chapiro, E, Gesk, S, Griffiths, M, Guttery, D, Haferlach, C, Harder, L, Heidenreich, O, Irving, J, Kearney, L, Nguyen-Khac, F, Machado, L, Minto, L, Majid, A, Moorman, A, Morrison, H, Rand, V, Strefford, J, Schwab, C, Tonnies, H, Dyer, M, Siebert, R & Harrison, C 2009, 'Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia', Blood, vol. 114, no. 13, pp. 2688-2698. https://doi.org/10.1182/blood-2009-03-208397

Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. / Russell, Lisa; Capasso, Melania; Vater, Inga; Akasaka, Takashui; Bernard, Olivier; Calasanz, Maria Jose; Chandrasekaran, Thiruppavaii; Chapiro, Elise; Gesk, Stephen; Griffiths, Mike; Guttery, David; Haferlach, Claudia; Harder, Lana; Heidenreich, Olaf; Irving, Julie; Kearney, Lyndal; Nguyen-Khac, Florence; Machado, Lee; Minto, Lynne; Majid, Aneela; Moorman, Anthony; Morrison, Heather; Rand, Vikki; Strefford, Jonathan; Schwab, Claire; Tonnies, Holger; Dyer, Martin; Siebert, Reiner; Harrison, Christine.

In: Blood, Vol. 114, No. 13, 29.07.2009, p. 2688-2698.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia

AU - Russell, Lisa

AU - Capasso, Melania

AU - Vater, Inga

AU - Akasaka, Takashui

AU - Bernard, Olivier

AU - Calasanz, Maria Jose

AU - Chandrasekaran, Thiruppavaii

AU - Chapiro, Elise

AU - Gesk, Stephen

AU - Griffiths, Mike

AU - Guttery, David

AU - Haferlach, Claudia

AU - Harder, Lana

AU - Heidenreich, Olaf

AU - Irving, Julie

AU - Kearney, Lyndal

AU - Nguyen-Khac, Florence

AU - Machado, Lee

AU - Minto, Lynne

AU - Majid, Aneela

AU - Moorman, Anthony

AU - Morrison, Heather

AU - Rand, Vikki

AU - Strefford, Jonathan

AU - Schwab, Claire

AU - Tonnies, Holger

AU - Dyer, Martin

AU - Siebert, Reiner

AU - Harrison, Christine

PY - 2009/7/29

Y1 - 2009/7/29

N2 - We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations

AB - We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations

U2 - 10.1182/blood-2009-03-208397

DO - 10.1182/blood-2009-03-208397

M3 - Article

VL - 114

SP - 2688

EP - 2698

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -