Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications

Sabina Chiaretti; Monica Messina; Sara Grammatico; Alfonso Piciocchi; Anna L. Fedullo; Filomena Di Giacomo; Nadia Peragine; Valentina Gianfelici; Alessia Lauretti; Rohan Bareja; Maria P. Martelli; Marco Vignetti; Valerio Apicella; Antonella Vitale; Loretta S. Li; Cyril Salek; Olivier Elemento; Giorgio Inghirami; David M. Weinstock; Anna Guarini; Robin Foà

doi:10.1111/bjh.15251

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications

Sabina Chiaretti^*, Monica Messina, Sara Grammatico, Alfonso Piciocchi, Anna L. Fedullo, Filomena Di Giacomo, Nadia Peragine, Valentina Gianfelici, Alessia Lauretti, Rohan Bareja, Maria P. Martelli, Marco Vignetti, Valerio Apicella, Antonella Vitale, Loretta S. Li, Cyril Salek, Olivier Elemento, Giorgio Inghirami, David M. Weinstock, Anna GuariniRobin Foà

^*Corresponding author for this work

Pediatrics

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

50 Scopus citations

Abstract

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values – assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical “BCR/ABL1-like predictor”, for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the “BCR/ABL1-like predictor”, we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.

Original language	English (US)
Pages (from-to)	642-652
Number of pages	11
Journal	British Journal of Haematology
Volume	181
Issue number	5
DOIs	https://doi.org/10.1111/bjh.15251
State	Published - Jun 2018

Funding

The authors wish to thank Associazione Italiana per la Ricerca sul Cancro (AIRC), Special Program Molecular Clinical Oncology-Extension program, 5 9 1000 (10007), Milan (Italy) to RF; Finanziamento per l’avvio alla ricerca 2015 (Sapienza University of Rome) to MM; Finanziamento Medi Progetti Universitari 2015 to SC (Sapienza University of Rome); Fondazione Le Molinette Onlus, Turin (Italy); MM was partly supported by Associazione Cristina Bassi Onlus (Genova). DMW is supported by NCI 5R01CA151898 and 5R01CA17238. SC designed research, analysed data and wrote the manuscript; MM performed experiments, analysed data and wrote the manuscript; SG performed experiments and analysed data; AP designed the BCR/ABL1-like predictor model and performed statistical analyses; ALF, VG, AL, NP performed experiments; FDG performed RNA sequencing experiments; MV performed statistical analyses; MPM, VA, AV and CS provided samples and clinico-biological data; OE and RB analysed RNA-sequencing data; LSL and DW provided clinical samples; GI analysed data and critically revised the manuscript; AG and RF designed the study, analysed data and critically revised the manuscript.

Keywords

Acute lymphoblastic leukaemia
BCR/ABL1-like
adults
prognosis
tyrosine kinase inhibitors

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/bjh.15251

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Chiaretti, S., Messina, M., Grammatico, S., Piciocchi, A., Fedullo, A. L., Di Giacomo, F., Peragine, N., Gianfelici, V., Lauretti, A., Bareja, R., Martelli, M. P., Vignetti, M., Apicella, V., Vitale, A., Li, L. S., Salek, C., Elemento, O., Inghirami, G., Weinstock, D. M., ... Foà, R. (2018). Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications. British Journal of Haematology, 181(5), 642-652. https://doi.org/10.1111/bjh.15251

@article{745bf0f626774bd5965aac4cda1fcb85,

title = "Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications",

abstract = "BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values – assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical “BCR/ABL1-like predictor”, for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the “BCR/ABL1-like predictor”, we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.",

keywords = "Acute lymphoblastic leukaemia, BCR/ABL1-like, adults, prognosis, tyrosine kinase inhibitors",

author = "Sabina Chiaretti and Monica Messina and Sara Grammatico and Alfonso Piciocchi and Fedullo, {Anna L.} and {Di Giacomo}, Filomena and Nadia Peragine and Valentina Gianfelici and Alessia Lauretti and Rohan Bareja and Martelli, {Maria P.} and Marco Vignetti and Valerio Apicella and Antonella Vitale and Li, {Loretta S.} and Cyril Salek and Olivier Elemento and Giorgio Inghirami and Weinstock, {David M.} and Anna Guarini and Robin Fo{\`a}",

note = "Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons Ltd",

year = "2018",

month = jun,

doi = "10.1111/bjh.15251",

language = "English (US)",

volume = "181",

pages = "642--652",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

Chiaretti, S, Messina, M, Grammatico, S, Piciocchi, A, Fedullo, AL, Di Giacomo, F, Peragine, N, Gianfelici, V, Lauretti, A, Bareja, R, Martelli, MP, Vignetti, M, Apicella, V, Vitale, A, Li, LS, Salek, C, Elemento, O, Inghirami, G, Weinstock, DM, Guarini, A & Foà, R 2018, 'Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications', British Journal of Haematology, vol. 181, no. 5, pp. 642-652. https://doi.org/10.1111/bjh.15251

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications. / Chiaretti, Sabina; Messina, Monica; Grammatico, Sara et al.
In: British Journal of Haematology, Vol. 181, No. 5, 06.2018, p. 642-652.

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

TY - JOUR

T1 - Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction

T2 - clinical, prognostic and therapeutic implications

AU - Chiaretti, Sabina

AU - Messina, Monica

AU - Grammatico, Sara

AU - Piciocchi, Alfonso

AU - Fedullo, Anna L.

AU - Di Giacomo, Filomena

AU - Peragine, Nadia

AU - Gianfelici, Valentina

AU - Lauretti, Alessia

AU - Bareja, Rohan

AU - Martelli, Maria P.

AU - Vignetti, Marco

AU - Apicella, Valerio

AU - Vitale, Antonella

AU - Li, Loretta S.

AU - Salek, Cyril

AU - Elemento, Olivier

AU - Inghirami, Giorgio

AU - Weinstock, David M.

AU - Guarini, Anna

AU - Foà, Robin

PY - 2018/6

Y1 - 2018/6

N2 - BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values – assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical “BCR/ABL1-like predictor”, for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the “BCR/ABL1-like predictor”, we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.

AB - BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values – assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical “BCR/ABL1-like predictor”, for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the “BCR/ABL1-like predictor”, we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.

KW - Acute lymphoblastic leukaemia

KW - BCR/ABL1-like

KW - adults

KW - prognosis

KW - tyrosine kinase inhibitors

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U2 - 10.1111/bjh.15251

DO - 10.1111/bjh.15251

M3 - Article

C2 - 29675955

AN - SCOPUS:85047562389

SN - 0007-1048

VL - 181

SP - 642

EP - 652

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 5

ER -

Chiaretti S, Messina M, Grammatico S, Piciocchi A, Fedullo AL, Di Giacomo F et al. Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications. British Journal of Haematology. 2018 Jun;181(5):642-652. doi: 10.1111/bjh.15251

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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