CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients: A single-institution experience

Sergej Konoplev; Xinyan Lu; Marina Konopleva; Nitin Jain; Juan Ouyang; Maitrayee Goswami; Kathryn G. Roberts; Marc Valentine; Charles G. Mullighan; Carlos Bueso-Ramos; Patrick A. Zweidler-McKay; Jeffrey L. Jorgensen; Sa A. Wang

doi:10.1093/AJCP/AQX005

CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients: A single-institution experience

Sergej Konoplev, Xinyan Lu, Marina Konopleva, Nitin Jain, Juan Ouyang, Maitrayee Goswami, Kathryn G. Roberts, Marc Valentine, Charles G. Mullighan, Carlos Bueso-Ramos, Patrick A. Zweidler-McKay, Jeffrey L. Jorgensen, Sa A. Wang^*

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Objectives: Cytokine receptor-like factor 2 (CRLF2) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2-cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%). Of CRLF2-cases, 21 (100%) of 21 cases showed CRLF2 rearrangement by fluorescence in situ hybridization, preferentially involving IGH@CRLF2 (15/15). The entire coding region of JAK2 was sequenced in 14 patients with CRLF2pB-ALL, and nine (64%) were positive for JAK2 mutations. Conclusions: MFC allows a rapid, inexpensive, and reliable detection of B-ALL with CRLF2 rearrangement that would further facilitate testing for JAK2 mutations for targetable therapy.

Original language	English (US)
Pages (from-to)	357-363
Number of pages	7
Journal	American journal of clinical pathology
Volume	147
Issue number	4
DOIs	https://doi.org/10.1093/AJCP/AQX005
State	Published - 2017

Keywords

B-lymphoblastic leukemia/lymphoma
BCR-ABL1-like
CRLF2
FISH
Flow cytometry
JAK2 mutation
Ph-like B-ALL

ASJC Scopus subject areas

Pathology and Forensic Medicine

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Konoplev, S., Lu, X., Konopleva, M., Jain, N., Ouyang, J., Goswami, M., Roberts, K. G., Valentine, M., Mullighan, C. G., Bueso-Ramos, C., Zweidler-McKay, P. A., Jorgensen, J. L., & Wang, S. A. (2017). CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients: A single-institution experience. American journal of clinical pathology, 147(4), 357-363. https://doi.org/10.1093/AJCP/AQX005

Konoplev, Sergej ; Lu, Xinyan ; Konopleva, Marina ; Jain, Nitin ; Ouyang, Juan ; Goswami, Maitrayee ; Roberts, Kathryn G. ; Valentine, Marc ; Mullighan, Charles G. ; Bueso-Ramos, Carlos ; Zweidler-McKay, Patrick A. ; Jorgensen, Jeffrey L. ; Wang, Sa A. / CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients : A single-institution experience. In: American journal of clinical pathology. 2017 ; Vol. 147, No. 4. pp. 357-363.

@article{4b6660954a02412d8228057b800109c8,

title = "CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients: A single-institution experience",

abstract = "Objectives: Cytokine receptor-like factor 2 (CRLF2) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2-cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%). Of CRLF2-cases, 21 (100%) of 21 cases showed CRLF2 rearrangement by fluorescence in situ hybridization, preferentially involving IGH@CRLF2 (15/15). The entire coding region of JAK2 was sequenced in 14 patients with CRLF2pB-ALL, and nine (64%) were positive for JAK2 mutations. Conclusions: MFC allows a rapid, inexpensive, and reliable detection of B-ALL with CRLF2 rearrangement that would further facilitate testing for JAK2 mutations for targetable therapy.",

keywords = "B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like, CRLF2, FISH, Flow cytometry, JAK2 mutation, Ph-like B-ALL",

author = "Sergej Konoplev and Xinyan Lu and Marina Konopleva and Nitin Jain and Juan Ouyang and Maitrayee Goswami and Roberts, {Kathryn G.} and Marc Valentine and Mullighan, {Charles G.} and Carlos Bueso-Ramos and Zweidler-McKay, {Patrick A.} and Jorgensen, {Jeffrey L.} and Wang, {Sa A.}",

year = "2017",

doi = "10.1093/AJCP/AQX005",

language = "English (US)",

volume = "147",

pages = "357--363",

journal = "American Journal of Clinical Pathology",

issn = "0002-9173",

publisher = "American Society of Clinical Pathologists",

number = "4",

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Konoplev, S, Lu, X, Konopleva, M, Jain, N, Ouyang, J, Goswami, M, Roberts, KG, Valentine, M, Mullighan, CG, Bueso-Ramos, C, Zweidler-McKay, PA, Jorgensen, JL & Wang, SA 2017, 'CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients: A single-institution experience', American journal of clinical pathology, vol. 147, no. 4, pp. 357-363. https://doi.org/10.1093/AJCP/AQX005

CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients : A single-institution experience. / Konoplev, Sergej; Lu, Xinyan; Konopleva, Marina; Jain, Nitin; Ouyang, Juan; Goswami, Maitrayee; Roberts, Kathryn G.; Valentine, Marc; Mullighan, Charles G.; Bueso-Ramos, Carlos; Zweidler-McKay, Patrick A.; Jorgensen, Jeffrey L.; Wang, Sa A.

In: American journal of clinical pathology, Vol. 147, No. 4, 2017, p. 357-363.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - CRLF2-positive B-cell acute lymphoblastic leukemia in adult patients

T2 - A single-institution experience

AU - Konoplev, Sergej

AU - Lu, Xinyan

AU - Konopleva, Marina

AU - Jain, Nitin

AU - Ouyang, Juan

AU - Goswami, Maitrayee

AU - Roberts, Kathryn G.

AU - Valentine, Marc

AU - Mullighan, Charles G.

AU - Bueso-Ramos, Carlos

AU - Zweidler-McKay, Patrick A.

AU - Jorgensen, Jeffrey L.

AU - Wang, Sa A.

PY - 2017

Y1 - 2017

N2 - Objectives: Cytokine receptor-like factor 2 (CRLF2) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2-cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%). Of CRLF2-cases, 21 (100%) of 21 cases showed CRLF2 rearrangement by fluorescence in situ hybridization, preferentially involving IGH@CRLF2 (15/15). The entire coding region of JAK2 was sequenced in 14 patients with CRLF2pB-ALL, and nine (64%) were positive for JAK2 mutations. Conclusions: MFC allows a rapid, inexpensive, and reliable detection of B-ALL with CRLF2 rearrangement that would further facilitate testing for JAK2 mutations for targetable therapy.

AB - Objectives: Cytokine receptor-like factor 2 (CRLF2) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2-cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%). Of CRLF2-cases, 21 (100%) of 21 cases showed CRLF2 rearrangement by fluorescence in situ hybridization, preferentially involving IGH@CRLF2 (15/15). The entire coding region of JAK2 was sequenced in 14 patients with CRLF2pB-ALL, and nine (64%) were positive for JAK2 mutations. Conclusions: MFC allows a rapid, inexpensive, and reliable detection of B-ALL with CRLF2 rearrangement that would further facilitate testing for JAK2 mutations for targetable therapy.

KW - B-lymphoblastic leukemia/lymphoma

KW - BCR-ABL1-like

KW - CRLF2

KW - FISH

KW - Flow cytometry

KW - JAK2 mutation

KW - Ph-like B-ALL

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DO - 10.1093/AJCP/AQX005

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