Prevalence and Clinical Outcome of Philadelphia-Like Acute Lymphoblastic Leukemia: Systematic Review and Meta-analysis

Abstract

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) has disease phenotypes similar to Ph D ALL. This meta-analysis aimed to include cohort study of patients with ALL who reported the prevalence of Ph-like ALL. Across the 15 included studies, the most common gene subgroup was CRLF2 gene rearrangement, and the peak prevalence of Ph-like ALL occurred in adolescents and young adults. Background: The presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Ph þ ALL, although the data are still inconclusive and the prevalence of Ph-like ALL varied considerably across studies. Patients and Methods: We performed a systematic review and meta-analysis in order to identify all cohort studies of patients with ALL that reported the prevalence of Ph-like ALL and to summarize their results together. The pooled prevalence and rate were calculated by the DerSimonian-Laird random-effect model with double arcsine transformation. Results: Across the 15 included studies describing 11,040 ALL patients, the peak prevalence of the presence of Ph-like ALL among patients with ALL was between ages 11 and 40 years, where the pooled prevalence was 25.8% to 26.2%. The pooled 5-year overall survival rate of Ph-like ALL was 42.8% (95% confidence interval, 23.9-64.1; I 2 93%). Comparative analysis with Bother ALL patients was conducted by the Mantel-Haenszel method; it found that Ph-like ALL patients had a significantly lower chance of being alive at 5 years (pooled odds ratio, 0.35; 95% confidence interval, 0.25-0.50; P < .00001, I 2 ¼ 40%). The chance of Ph-like ALL patients surviving at 5 years was similar to Ph-positive ALL patients (pooled odds ratio, 0.72; 95% confidence interval, 0.26-2.02; P ¼ .53, I 2 ¼ 77%). Conclusion: Ph-like ALL is not uncommon among ALL patients, and its presence is associated with an unfavorable outcome. More investigations are needed for better therapeutic options.

Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia

“…One such example is Philadelphia-chromosome-like ALL (Ph-like ALL), or BCR-ABL1 -like ALL, is a high-risk subtype of B-cell ALL (B-ALL) defined by a transcriptomic signature similar to BCR-ABL1 -positive ALL but lacking the BCR-ABL1 translocation 9 , 10 . Ph-like ALL occurs in 15% of childhood B-ALL cases, with peak incidence among adolescents and young adults, and is characterized by genomic alterations in cytokine or kinase signaling pathways, and crucial lymphoid transcription factor genes 11 , 12 .…”

Acute Lymphoblastic Leukemia in Adolescents and Young Adults

“…By age subgroup the reported prevalence was: 1-10 years 15.6%, 10-20 years 25.6%, 21-40 years of age 26.2% and in the group over 40 years of age 16.9%. In this meta-analysis, the overall 5-year survival rate was 42.8% (CI 95% CI, 23.9-64.1, I2 93) [83].…”

The Role Played by Wnt/β-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia

“…Last, but not least, the Wnt/β-catenin network is dysregulated in Philadelphia positive (Ph + ) B-ALL, which is a leukemia subset characterized by an extremely poor outcome [99]. In Ph + B-ALL, the over-activation of Wnt/β-catenin pathway in B-ALL may be caused by epigenetic alterations, including hypermethylation of promoters of the Wnt/β-catenin antagonists SFRP, WIF1, and Dkk3 [100].…”