Philadelphia Chromosome–like Acute Lymphoblastic Leukemia
TLDR
Although most patients with Ph‐like ALL have positive minimal residual disease after remission induction and poor event‐free survival, approximately 40% of pediatric patients responded well to chemotherapy and can be cured with relatively low intensity of treatment.Abstract:
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described B-cell precursor ALL with a gene expression profile and a high frequency of IKZF1 gene alteration similar to that of Ph-positive ALL. Its prevalence is approximately 12% in children, 21% in adolescents (16-20 years of age), and 20% to 24% in adults older than 40 years, with a peak (27%) in young adults 21 to 39 years old. It occurs more often in male individuals and patients with Down syndrome. Ph-like ALL is overrepresented in those with Hispanic ethnicity and is associated with inherited genetic variants in GATA3 (rs3824662). It is a clinically and biologically heterogeneous subtype of B-ALL. Although most patients with Ph-like ALL have positive minimal residual disease after remission induction and poor event-free survival, approximately 40% of pediatric patients responded well to chemotherapy and can be cured with relatively low intensity of treatment. The treatment outcome correlated negatively with increasing age at presentation. Ph-like ALL is characterized by a wide range of genetic alterations that dysregulate several cytokine receptor and kinase signaling pathways, including CRLF2 rearrangement in half of the cases and translocation of nonreceptor tyrosine kinases (predominantly ABL-class and Janus kinases). Patients with ABL-class fusions respond clinically to ABL1 tyrosine kinase inhibitors, whereas mutations activating the JAK-STAT pathway are amendable to treatment with JAK inhibitors in vitro or in preclinical models. Prospective studies are needed to determine if incorporation of tyrosine kinase inhibitor targeting kinase alterations into intensive chemotherapy regimens will improve outcome of patients with Ph-like ALL.read more
Citations
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Journal ArticleDOI
Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults
Nitin Jain,Kathryn G. Roberts,Elias Jabbour,Keyur P. Patel,Agda Karina Eterovic,Ken Chen,Patrick A. Zweidler-McKay,Xinyan Lu,Gloria L. Fawcett,Sa A. Wang,Sergej Konoplev,Richard C. Harvey,I-Ming Chen,Debbie Payne-Turner,Marcus B. Valentine,Deborah A. Thomas,Guillermo Garcia-Manero,Farhad Ravandi,Jorge E. Cortes,Steven M. Kornblau,Susan O'Brien,Sherry Pierce,Jeffrey L. Jorgensen,Kenna R. Mills Shaw,Cheryl L. Willman,Charles G. Mullighan,Hagop M. Kantarjian,Marina Konopleva +27 more
TL;DR: High frequency ofPh-like ALL in adults, an increased frequency of Ph-like All in adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph- like ALL, and significantly worse outcomes in the CRLF2+ subset of Ph -like ALL are shown.
Journal ArticleDOI
Somatic and germline genomics in paediatric acute lymphoblastic leukaemia
TL;DR: Advances in genomic research and risk-directed therapy have led to improvements in the long-term survival and quality of life outcomes of patients with childhood acute lymphoblastic leukaemia, but a growing number of genetic conditions that predispose patients to develop ALL have been identified.
Journal ArticleDOI
Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia.
David T. Teachey,Ching-Hon Pui +1 more
TL;DR: Novel treatments under investigation might narrow the gap in survival between T- cell ALL and B-cell ALL, although novel treatment options for T-cell All are limited.
Journal ArticleDOI
Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements
Ilaria Tanasi,Ibrahima Ba,Nicolas Sirvent,Thorsten Braun,Wendy Cuccuini,Paola Ballerini,Nicolas Duployez,Aline Tanguy-Schmidt,Jerome Tamburini,Sébastien Maury,E. Dore,Chantal Himberlin,Cédric Duclos,Patrice Chevallier,Philippe Rousselot,Massimiliano Bonifacio,Hélène Cavé,André Baruchel,Hervé Dombret,Jean Soulier,Judith Landman-Parker,Nicolas Boissel,Emmanuelle Clappier +22 more
TL;DR: A prospective strategy for identifying patients with Philadelphia-like acute lymphoblastic leukemia is presented, demonstrating the efficacy of early introduction of tyrosine kinase inhibitors in improving outcomes.
Journal ArticleDOI
Global efforts toward the cure of childhood acute lymphoblastic leukaemia.
TL;DR: The greatest obstacle to overcome will be to fully understand leukaemogenesis, enabling measures to decrease the risk of leukaemia development and thus close the last major gap in offering a cure to any child who might have the disease.
References
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Journal ArticleDOI
Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
Charles G. Mullighan,Xiaoping Su,Jinghui Zhang,Ina Radtke,Letha A. Phillips,Christopher B. Miller,Jing Ma,Wei Liu,Cheng Cheng,Brenda A. Schulman,Brenda A. Schulman,Richard C. Harvey,Richard C. Harvey,I-Ming Chen,I-Ming Chen,Robert J. Clifford,William L. Carroll,Gregory H. Reaman,W. Paul Bowman,Meenakshi Devidas,Daniela S. Gerhard,Wenjian Yang,Mary V. Relling,Sheila A. Shurtleff,Dario Campana,Michael J. Borowitz,Ching-Hon Pui,Malcolm A. Smith,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,James R. Downing +31 more
TL;DR: In this paper, a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis were studied.
Journal ArticleDOI
Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia
Kathryn G. Roberts,Yongjin Li,Debbie Payne-Turner,Richard C. Harvey,Yung-Li Yang,Dehua Pei,Kelly McCastlain,Li Ding,Li Ding,Changxue Lu,Changxue Lu,Guangchun Song,Jing Ma,Jared Becksfort,Michael Rusch,S. C. Chen,John Easton,J. Cheng,Kristy Boggs,Natalia Santiago-Morales,Ilaria Iacobucci,Robert S. Fulton,Robert S. Fulton,Ji Wen,Marcus B. Valentine,Cheng Cheng,Steven W. Paugh,Meenakshi Devidas,Meenakshi Devidas,I-Ming Chen,S. Reshmi,S. Reshmi,Amy Smith,Erin Hedlund,Pankaj Gupta,Panduka Nagahawatte,Gang Wu,Xiang Chen,Donald Yergeau,Bhavin Vadodaria,Heather L. Mulder,Naomi J. Winick,Eric Larsen,William L. Carroll,William L. Carroll,Nyla A. Heerema,Andrew J. Carroll,G. Grayson,Sarah K. Tasian,Andrew S. Moore,F. Keller,Melissa Frei-Jones,J. A. Whitlock,Elizabeth A. Raetz,Deborah L. White,Timothy P. Hughes,J. M. Guidry Auvil,Malcolm A. Smith,Malcolm A. Smith,Guido Marcucci,Clara D. Bloomfield,Krzysztof Mrózek,Jessica Kohlschmidt,Jessica Kohlschmidt,Wendy Stock,Steven M. Kornblau,Marina Konopleva,Elisabeth Paietta,Ching-Hon Pui,Sima Jeha,Mary V. Relling,William E. Evans,Daniela S. Gerhard,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Elaine R. Mardis,Richard K. Wilson,Mignon L. Loh,Mignon L. Loh,James R. Downing,James R. Downing,Stephen P. Hunger,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,Jinghui Zhang,Charles G. Mullighan,Charles G. Mullighan +87 more
TL;DR: Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors.
Journal ArticleDOI
BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros
Charles G. Mullighan,Christopher B. Miller,Ina Radtke,Letha A. Phillips,James T. Dalton,Jing Ma,Deborah L. White,Timothy P. Hughes,Michelle M. Le Beau,Ching-Hon Pui,Mary V. Relling,Sheila A. Shurtleff,James R. Downing +12 more
TL;DR: Genetic lesions resulting in the loss of Ikaros function are an important event in the development of BCR–ABL1 ALL, according to genome-wide analysis of diagnostic leukaemia samples.
Journal ArticleDOI
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study
Monique L. den Boer,Marjon van Slegtenhorst,Renee X. de Menezes,Renee X. de Menezes,Meyling Cheok,Jessica Buijs-Gladdines,Susan T C J M Peters,Laura J. C. M. van Zutven,H. Berna Beverloo,Peter J. van der Spek,Gaby Escherich,Martin A. Horstmann,Gritta Janka-Schaub,Willem A. Kamps,William E. Evans,Rob Pieters +15 more
TL;DR: A genome-wide study to improve prognostic classification of ALL in children revealed a new ALL subtype, the underlying genetic abnormalities of which were characterised by comparative genomic hybridisation-arrays and molecular cytogenetics.
Journal ArticleDOI
Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia
Kathryn G. Roberts,Ryan D. Morin,Jinghui Zhang,Martin Hirst,Yongjun Zhao,Xiaoping Su,Shann-Ching Chen,Debbie Payne-Turner,Michelle L. Churchman,Richard C. Harvey,Xiang Chen,Corynn Kasap,Chunhua Yan,Jared Becksfort,Richard Finney,David T. Teachey,Shannon L. Maude,Kane Tse,Richard A. Moore,Steven J.M. Jones,Karen Mungall,Inanc Birol,Michael N. Edmonson,Ying Hu,Kenneth E Buetow,I-Ming Chen,William L. Carroll,Lei Wei,Jing Ma,Maria Kleppe,Ross L. Levine,Guillermo Garcia-Manero,Eric Larsen,Neil P. Shah,Meenakshi Devidas,Gregory H. Reaman,Malcolm A. Smith,Steven W. Paugh,William E. Evans,Stephan A. Grupp,Sima Jeha,Ching-Hon Pui,Daniela S. Gerhard,James R. Downing,Cheryl L. Willman,Mignon L. Loh,Stephen P. Hunger,Marco A. Marra,Marco A. Marra,Charles G. Mullighan +49 more
TL;DR: Several genetic alterations that activate kinase signaling in Ph-like ALL induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.
Related Papers (5)
Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia
Kathryn G. Roberts,Yongjin Li,Debbie Payne-Turner,Richard C. Harvey,Yung-Li Yang,Dehua Pei,Kelly McCastlain,Li Ding,Li Ding,Changxue Lu,Changxue Lu,Guangchun Song,Jing Ma,Jared Becksfort,Michael Rusch,S. C. Chen,John Easton,J. Cheng,Kristy Boggs,Natalia Santiago-Morales,Ilaria Iacobucci,Robert S. Fulton,Robert S. Fulton,Ji Wen,Marcus B. Valentine,Cheng Cheng,Steven W. Paugh,Meenakshi Devidas,Meenakshi Devidas,I-Ming Chen,S. Reshmi,S. Reshmi,Amy Smith,Erin Hedlund,Pankaj Gupta,Panduka Nagahawatte,Gang Wu,Xiang Chen,Donald Yergeau,Bhavin Vadodaria,Heather L. Mulder,Naomi J. Winick,Eric Larsen,William L. Carroll,William L. Carroll,Nyla A. Heerema,Andrew J. Carroll,G. Grayson,Sarah K. Tasian,Andrew S. Moore,F. Keller,Melissa Frei-Jones,J. A. Whitlock,Elizabeth A. Raetz,Deborah L. White,Timothy P. Hughes,J. M. Guidry Auvil,Malcolm A. Smith,Malcolm A. Smith,Guido Marcucci,Clara D. Bloomfield,Krzysztof Mrózek,Jessica Kohlschmidt,Jessica Kohlschmidt,Wendy Stock,Steven M. Kornblau,Marina Konopleva,Elisabeth Paietta,Ching-Hon Pui,Sima Jeha,Mary V. Relling,William E. Evans,Daniela S. Gerhard,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Elaine R. Mardis,Richard K. Wilson,Mignon L. Loh,Mignon L. Loh,James R. Downing,James R. Downing,Stephen P. Hunger,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,Jinghui Zhang,Charles G. Mullighan,Charles G. Mullighan +87 more
Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
Charles G. Mullighan,Xiaoping Su,Jinghui Zhang,Ina Radtke,Letha A. Phillips,Christopher B. Miller,Jing Ma,Wei Liu,Cheng Cheng,Brenda A. Schulman,Brenda A. Schulman,Richard C. Harvey,Richard C. Harvey,I-Ming Chen,I-Ming Chen,Robert J. Clifford,William L. Carroll,Gregory H. Reaman,W. Paul Bowman,Meenakshi Devidas,Daniela S. Gerhard,Wenjian Yang,Mary V. Relling,Sheila A. Shurtleff,Dario Campana,Michael J. Borowitz,Ching-Hon Pui,Malcolm A. Smith,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,James R. Downing +31 more
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study
Monique L. den Boer,Marjon van Slegtenhorst,Renee X. de Menezes,Renee X. de Menezes,Meyling Cheok,Jessica Buijs-Gladdines,Susan T C J M Peters,Laura J. C. M. van Zutven,H. Berna Beverloo,Peter J. van der Spek,Gaby Escherich,Martin A. Horstmann,Gritta Janka-Schaub,Willem A. Kamps,William E. Evans,Rob Pieters +15 more
Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia.
Charles G. Mullighan,J. Racquel Collins-Underwood,Letha A. Phillips,Michael G. Loudin,Wei Liu,Jinghui Zhang,Jing Ma,Elaine Coustan-Smith,Richard C. Harvey,Cheryl L. Willman,Fady M. Mikhail,Julia Meyer,Andrew J. Carroll,Richard T. Williams,Jinjun Cheng,Nyla A. Heerema,Giuseppe Basso,Andrea Pession,Ching-Hon Pui,Susana C. Raimondi,Stephen P. Hunger,James R. Downing,William L. Carroll,Karen R. Rabin +23 more
The genomic landscape of hypodiploid acute lymphoblastic leukemia
Linda Holmfeldt,Lei Wei,Ernesto Diaz-Flores,Michael Walsh,Jinghui Zhang,Li Ding,Debbie Payne-Turner,Michelle L. Churchman,Anna Andersson,Shann Ching Chen,Kelly McCastlain,Jared Becksfort,Jing Ma,Gang Wu,Samir Patel,Susan L. Heatley,Letha A. Phillips,Guangchun Song,John Easton,Matthew Parker,Xiang Chen,Michael Rusch,Kristy Boggs,Bhavin Vadodaria,Erin Hedlund,Christina D. Drenberg,Sharyn D. Baker,Deqing Pei,Cheng Cheng,Robert Huether,Charles Lu,Robert S. Fulton,Lucinda Fulton,Yashodhan Tabib,David J. Dooling,Kerri Ochoa,Mark D. Minden,Ian D. Lewis,L. Bik To,Paula Marlton,Andrew W. Roberts,Gordana Raca,Wendy Stock,Geoffrey Neale,Hans G. Drexler,Ross A. Dickins,David W. Ellison,Sheila A. Shurtleff,Ching-Hon Pui,Raul C. Ribeiro,Meenakshi Devidas,Andrew J. Carroll,Nyla A. Heerema,Brent L. Wood,Michael J. Borowitz,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Susana C. Raimondi,Elaine R. Mardis,Richard K. Wilson,James R. Downing,Stephen P. Hunger,Mignon L. Loh,Charles G. Mullighan +63 more