High incidence of Philadelphia chromosome-like acute lymphoblastic leukemia in older adults with B-ALL

Sk, Tasian; Hurtz, Christian; Gb, Wertheim; Bailey, Nathanael G.; Ms, Lim; Harvey, Richard C.; Chen, IM; Cl, Willman; Astles, Rachel; Zebrowski, Alexis; Reshmi, SC; Mm, Li; Nv, Frey; Luger, SM; Carroll, Martin; Ae, Perl

doi:10.1038/leu.2016.375

Cited by 86 publications

(67 citation statements)

References 15 publications

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“…It comprises approximately 12% of children with B-cell precursor ALL (10% of NCI standard-risk and 13% to 14% of NCI high-risk BALL), 21% of adolescents 16 to 20 years old, 27% of young adults 21 to 39 years old, and 20% to 24% of older adults above 40 years old. 8,11–13 (Table 1) Compared to Ph-positive ALL, the prevalence of Ph-like ALL is 3 to 4 times more common in children and approximately the same as that in adults. A higher proportion of patients with Ph-like ALL are males compared to those with non-Ph-like B-ALL in both children and adults with a male-to-female ratio of 2:1 and 1.6:1, respectively.…”

Section: Prevalence and Clinical Featuresmentioning

confidence: 99%

Philadelphia Chromosome–like Acute Lymphoblastic Leukemia

Pui

Roberts

Yang

et al. 2017

Clinical Lymphoma Myeloma and Leukemia

104

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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 to 20 years of age) and 20% to 24% in older adults above the age of 40 years old, with a peak (27%) in young adults 21 to 39 years old. It occurs more often in males 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. While 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 non-receptor tyrosine kinases (predominantly ABL-class and Janus kinases). Patients with ABL-class fusions respond clinically to ABL1 tyrosine kinase inhibitors, whilst 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.

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Section: Prevalence and Clinical Featuresmentioning

confidence: 99%

Philadelphia Chromosome–like Acute Lymphoblastic Leukemia

Pui

Roberts

Yang

et al. 2017

Clinical Lymphoma Myeloma and Leukemia

104

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“…Subsequently, CRLF2 overexpression was linked to the BCR/ABL1 –like profile; it was detected in approximately 24% of pediatric patients with standard‐risk BCR/ABL1– like ALL and in 55% of high‐risk pediatric patients . In adolescent and adult patients with BCR/ABL1 –like ALL, CRLF 2 overexpression is reported to be detected in approximately 50% to 60% of cases . P2RY8/CRLF2 prevails in children, whereas IGH/CRLF2 is more frequent in adolescents and adults, which is in agreement with the increased incidence of other IGH rearrangements reported in the older ALL population …”

Section: Introductionmentioning

confidence: 99%

BCR/ABL1–like acute lymphoblastic leukemia: How to diagnose and treat?

Chiaretti

Messina

Foà

2018

Cancer

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BCR/ABL1–like acute lymphoblastic leukemia (ALL) accounts for 15% to 30% of B‐lineage ALL, with a peak of incidence occurring in adolescence. This subgroup of patients is characterized by a peculiar transcriptional profile that resembles that of true BCR/ABL1–positive cases, and have a heterogeneous genetic background and a poor outcome. Next‐generation sequencing studies have demonstrated that the majority of patients carry rearrangements of tyrosine kinases or cytokine receptors and mutations of janus kinase (JAK)/signal transducer and activator of transcription (STAT), thus opening the way to the possible use of targeted therapeutic approaches. However, several issues remain unresolved at both the diagnostic and therapeutic level, such as the definition of a standardized method to identify BCR/ABL1–like ALL and the design of ad hoc clinical trials examining tyrosine kinase inhibitors or other tailored treatments. These aspects are discussed in this review.

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“…It has characteristic and distinct genetic mutations and rearrangements that are activated by a diverse array of cytokine receptor and tyrosine kinase signaling [87,89,[92][93][94]96]. The genetic lesions in adults with Ph-like ALL resembles that in children with Ph-like ALL but differs from the profile in the remaining patients with pre-B ALL [99].…”

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

“…When compared to other pre-B ALL subtypes, Ph-like ALL has the following characteristic features: (1) higher median leukocyte count at presentation, (2) higher median levels of MRD at the end of induction therapy, (3) inferior estimated event-free survival (EFS) at 5 years [58% versus (vs.) 84% in children, 41% vs. 83% in adolescents and 24% vs 63% in young adults], and (4) inferior estimated OS at 5 years [73% vs. 92% in children, 66% vs. 93% in adolescents and 26% vs 75% in young adults [88]. The various genetic abnormalities that are encountered in patients with Ph-like ALL and their targeted therapies are shown in Table 8 [19,[93][94][95][96][97] The investigational targeted therapies in Ph-like ALL are shown in Table 9 [89,98].…”

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

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Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Wk¹,

Dridi²,

Ka³

2017

J Mol Genet Med

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The recent improvements in the outcomes of patients with acute lymphoblastic leukemia reflect the progress in the field of diagnostics and the achievements in therapeutic interventions. In particular, the availability of more advanced technology in the cytogenetic and molecular laboratories has resulted in the stratification of patients into specific risk groups and thus several novel agents as well as targeted therapies have been introduced. Additionally, precision medicine will be applicable in the near future and thus the recent developments will facilitate the provision of safer modalities of therapy that may ultimately yield not only higher responses but also improved survival rates.This review represents a recent update on the role of various cytogenetic assays and molecular techniques in patients with acute lymphoblastic leukemia. It is composed of a number of sections including: history of cytogenetics, disease etiology and pathophysiology, utilization of various cytogenetic assays diagnostically, disease-specific cytogenetic and molecular abnormalities, common disease genetic subtypes, prognosis and risk stratification, refractory and relapsed disease, novel therapies, precision medicine and drug repurposing.

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High incidence of Philadelphia chromosome-like acute lymphoblastic leukemia in older adults with B-ALL

Cited by 86 publications

References 15 publications

Philadelphia Chromosome–like Acute Lymphoblastic Leukemia

Philadelphia Chromosome–like Acute Lymphoblastic Leukemia

BCR/ABL1–like acute lymphoblastic leukemia: How to diagnose and treat?

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

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