Ph-like acute lymphoblastic leukemia

Tran, Thai Hoa; Loh, Mignon L.

doi:10.1182/asheducation-2016.1.561

Cited by 72 publications

(87 citation statements)

References 41 publications

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“…Ph-like ALL can be detected in approximately: 10%-15% of children, 20%-25% of adolescents and 20%-23% of adults with B-cell ALL [88,[90][91][92]. It is encountered more frequently in male adults and has associations with: Hispanic ethnicity, Down's syndrome and inherited genetic variants in GATA3 (rs3824662) [91,92].…”

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

“…It is encountered more frequently in male adults and has associations with: Hispanic ethnicity, Down's syndrome and inherited genetic variants in GATA3 (rs3824662) [91,92]. 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].…”

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

“…Unfortunately, Ph-like ALL is essentially heterogeneous and a HR subtype of ALL [19,[92][93][94][95]98]. 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].…”

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

“…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%

“…Ph-like ALL is associated: with resistance to cytotoxic chemotherapy, very high risk of disease relapse and poor OS [88,90,92,93,95,96,98,99]. The identification of a wide range of genetic alterations that activate certain signaling pathways makes such gene alterations amenable to inhibition by a variety of TKIs [97].…”

Section: Page 8 Of 15mentioning

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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Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

Section: Philadelphia Chromosome-like Allmentioning

confidence: 99%

Section: Page 8 Of 15mentioning

confidence: 99%

See 3 more Smart Citations

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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References

2021

Flow Cytometry of Hematological Malignancies

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Philadelphia chromosome‐like acute lymphocytic leukemia: Perspectives on diagnosis

Prescott

Stock

2019

Adv Cell Gene Ther

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Philadelphia chromosome-like acute lymphocytic leukemia (Ph-L ALL) is a heterogenous subset of ALL defined within the past decade. As its name implies, this entity shares a similar gene expression profile (GEP) with Philadelphia chromosome positive ALL (Ph+ ALL), but lacks the BCR-ABL1 fusion. 1-3 This similarity in GEP is due to the presence of kinase activations, usually resulting from the presence of chromosomal micro-deletions and insertions that result in oncogenic fusions that drive the development of both types of leukemia. 4-7 The vast majority of Ph-L ALL cases contain at least one activating kinase alteration and, as with Ph+ ALL, >70% of Ph-L ALL cases possess defects in the transcription factor IKZF1. 8-10 Defects in IKZF1 are associated with the development of B-cell precursor ALL (BCP-ALL) and, more specifically, high risk BCP-ALL that possess activated tyrosine kinase profiles. Interestingly, IKZF1 mutations have been described to affect downstream signaling pathways that ultimately result in treatment resistance and poor response to conventional chemotherapy. 9 It is not surprising then, that a large majority of both Ph-L and Ph+ ALL contain these mutations. Unlike Ph+ ALL, however, as mentioned above, this subset lacks the classic t[9;22].It should be noted that Ph-L ALL is an umbrella term and by no means defines a single entity. Not only is this disease subset characterized by a wide array of potentially targetable kinase and cytokine rearrangements, the definition of Ph-L ALL itself is not standardized-with the gold standard diagnosis consisting of 2 different probe sets. 1,8,11 It may be best to think of Ph-L ALL as a group of BCP-ALL that shows poor response to conventional chemotherapy with persistence of minimal residual disease and, as with Ph+ ALL, contains potentially therapeutically targetable genetic alterations. Generally speaking, Ph-L ALL can be further divided into 3 broad groups: ABL class fusions (consisting of rearrangements in ABL1, ABL2, CSF1R, PDGFRB), JAK/STAT pathway alterations (consisting of CRLF2 ± JAK mutation, isolated JAK 1-3 mutations, EPOR, IL2RB, TSLP), and a miscellaneous category consisting of a multitude of less common rearrangements, including Ras pathway mutations. 3,4,8 The frequency of these mutations varies by age group. While always more predominant than other subtypes of Ph-L ALL, alterations in the JAK/STAT pathway (including CRLF2 overexpression) occur more frequently with advancing age from pediatric to the young and older adult populations. The converse is true of ABL class fusions, with a decline in frequency as we progress from pediatric to adult subgroups. 3,10 Averaged among all age groups, alterations in the JAK/ STAT pathway are seen in >70% of Ph-L ALL cases, with ABL class fusions occurring in roughly 10% of cases. 3,12 Thus, a significant majority of Ph-L ALL could, at least in theory, be managed with JAK inhibitors (JAKi) and ABL inhibitors (ABLi). Individuals with Ph-L ALL tend to have higher WBC counts at diagnosis, higher rates of induct...

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Ph-like acute lymphoblastic leukemia

Cited by 72 publications

References 41 publications

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

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

References

Philadelphia chromosome‐like acute lymphocytic leukemia: Perspectives on diagnosis

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