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There are few data on the incidence, characterization, and treatment outcomes of Ph\u2010like ALL cases from low\u2010 and middle\u2010income countries. There is a pressing need to establish a well\u2010organized\/cost\u2010effective approach for identifying Ph\u2010like ALL instances.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph\u2010like ALL cases among recurrent genetic abnormalities (RGA)<jats:sup>neg<\/jats:sup> B\u2010ALL cases. At the end of induction therapy, flow cytometry\u2010minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph\u2010like ALL cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 130 newly diagnosed B\u2010ALL cases, 25% (<jats:italic>BCR::ABL1<\/jats:italic>), 4% (<jats:italic>ETV6::RUNX1<\/jats:italic>), 5% (<jats:italic>TCF3::PBX1<\/jats:italic>), 2% (<jats:italic>KM2TA::AFF1<\/jats:italic>), and 65% RGA<jats:sup>neg<\/jats:sup> B\u2010ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGA<jats:sup>neg<\/jats:sup> B\u2010ALL cases, 24% Ph\u2010like ALL cases using nCounter NanoString were identified, with 48% <jats:italic>CRLF2<\/jats:italic><jats:sup>high<\/jats:sup> cases with 45% <jats:italic>CRLF2::P2RY8<\/jats:italic> and 18% <jats:italic>CRLF2::IGH<\/jats:italic> rearrangements(\u223cr) revealed by fluorescence in situ hybridization. In 52% of <jats:italic>CRLF2<\/jats:italic><jats:sup>low<\/jats:sup> cases, 17% <jats:italic>ABL1<\/jats:italic> and JAK2\u223cr 8% <jats:italic>EPOR::IGH<\/jats:italic> &amp; <jats:italic>PDGRFB<\/jats:italic>\u223cr were identified. Ph\u2010like ALL cases had higher total leukocyte count (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05), male preponderance (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05), and high MRD\u2010positivity\/induction failure compared with RGA<jats:sup>neg<\/jats:sup> B\u2010ALL cases. Furthermore, in Ph\u2010like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. <jats:italic>CRLF2, IGJ, CEACAM6, MUC4, SPATS2L<\/jats:italic> and <jats:italic>NRXN3<\/jats:italic> genes were overexpressed and show statistical significance (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) in Ph\u2010like ALL cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study showed the high incidence of Ph\u2010like ALL cases with kinase activating alterations and treatment outcomes from low\u2010 and middle\u2010income region. Furthermore, a surrogate cost\u2010effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph\u2010like ALL cases is proposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Identification of recurrent gene abnormalities (RGA)<jats:sup>neg<\/jats:sup> B\u2010acute lymphoblastic leukemia (B\u2010ALL) cases using multiplex\u2010reverse transcriptase polymerase chain reaction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Identification and characterization of Philadelphia (Ph)\u2013like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Furthermore, Ph\u2010like ALL cases were characterized according to CRLF2 expression and kinase\u2010activating genomic alterations. Minimal residual disease of Ph\u2010like ALL cases were quantified using flow cytometry\u2010minimal residual disease assay.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A surrogate molecular approach was established to detect Ph\u2010like ALL cases from low\u2010 and middle\u2010income countries.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35051","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:50:26Z","timestamp":1697075426000},"page":"713-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A surrogate molecular approach for the detection of Philadelphia chromosome\u2013like B\u2010acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9449-7585","authenticated-orcid":false,"given":"Dikshat Gopal","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Urology &amp; Pathology The Robert H. 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