{"doi":"10.1002/ajh.25729","title":"Clinical utility of fluorescence in situ hybridization‐based diagnosis of <i>BCR‐ABL1</i> like (<scp>P</scp>hiladelphia chromosome like) <scp>B</scp>‐acute lymphoblastic leukemia","abstract":"To the Editor: The outcomes of patients with B acute lymphoblastic leukemia (B-ALL) have improved over the past few decades, mainly due to the adaptation of therapy based on risk that incorporates recurrent primary cytogenetic subtypes along with clinical risk factors for relapse. However, long term overall survival (OS) rates of B-ALL in adults remain low, with 5-year OS 20-40%,1 whereas 5-year OS is over 85% in children.2 Note, BCR-ABL1-like ALL (Ph-like ALL) is a recently characterized high risk subtype, recognized as a provisional entity in the World Health Organization (WHO), that primarily affects children and young adults.3 It was initially defined by a gene expression profile similar to that of Ph (+) ALL that activates tyrosine kinase (TK) or cytokine receptor signaling. The incidence of Ph-like ALL varies between 20-35% in different studies. Several studies have described inferior outcomes with conventional chemotherapy and long term survival rates are 10-35%.3 There are two different groups of genetic alterations described in Ph-like ALL; ABL-class fusions that phenocopy BCR-ABL1, involving ABL1, ABL2, CSF1R and PDGFRB and gene rearrangements that activate JAK/STAT signaling, including alterations of CRFL2, JAK2 and EPOR.4 In prior studies, approximately half of the cases with Ph-like ALL had a CRLF2 rearrangement and over half of those had concomitant JAK1 or JAK2 mutations.4, 5 Other common alterations were non-BCR ABL-gene fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), JAK/STAT sequence mutations (7.2%), other kinase alterations (4.1%) and RAS pathway mutations (3.6%). Importantly, the majority of these alterations were potentially targetable with TKIs, JAK inhibitors or inhibitors of ALK.5 Thus, despite the complexity of multiple genetic alterations in Ph-like ALL, most of those can be identified with standard molecular and cytogenetic approaches and have therapeutic potential. We have designed a fluorescence in situ hybridization (FISH) panel with probes targeting most therapeutically relevant rearrangements seen in Ph-like ALL. The purpose of designing an in-house FISH panel is to provide a rapid test to detect the Ph-like abnormalities in patients that could potentially benefit from the addition of TKIs or JAK-inhibitors to conventional chemotherapy. In this study, we aimed to assess the utility of our in-house FISH panel in a cohort of Ph (−) B-ALL patients. We retrospectively identified all patients with Ph (−) B-ALL in a clinically annotated database of patients with B-ALL treated at Mayo Clinic Rochester from 1995-2017. Both adult and pediatric patients were included. Adolescent and young adults (AYA) were defined as patients 15-39 years of age. With FISH, a targeted Ph-like ALL panel was retrospectively performed in all cases, with available fixed frozen bone marrow cell pellets at the time of diagnosis (n = 112), in the Mayo Clinic Cytogenetics Core Laboratory. This FISH panel was developed by our Clinical Genomics Laboratory in order to identify Ph-like arrangements and included the following probes: 1) BCR-ABL1 for ABL1 abnormalities. If additional ABL1 signals not fused with BCR were identified, an ABL1 break apart probe was utilized to detect a potential ABL1 rearrangement, 2) t(1q25;var) for ABL2 rearrangements, 3) t(5q33;var) for PDGFRB or CSF1R rearrangements (Figure S1), 4) t(9p24.1;var) for JAK2 rearrangements, 5) t(Xp22.3;var) or t(Yp11.32;var) for CRLF2 rearrangements (Cytocell, NY). Reflex probes for CRLF2 rearrangements included a double fusion strategy for: 1) t(X;14)(p22.3;q32) or t(Y;14)(p11.32;q32) for CRLF2/IGH fusion, or 2) t(Xp22.3;var) or t(Yp11.32;var) for P2RY8 rearrangements (Cytocell, NY). Mate pair sequencing (MPseq) was performed on three specimens (patients two, seven, and eight) to further clarify two CRLF2/P2RY8 abnormalities and an atypical JAK2 abnormality. The OS was defined as time from diagnosis until death or last follow-up. Treatment-Free Survival (TFS) was def","journal":"American Journal of Hematology","year":2020,"id":110317,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526261,"name":"Ryan A. Knudson","orcid":null,"position":1,"is_corresponding":false},{"id":524727,"name":"Kathryn E. Pearce","orcid":null,"position":2,"is_corresponding":false},{"id":526262,"name":"Reid G. Meyer","orcid":null,"position":3,"is_corresponding":false},{"id":251186,"name":"Beth A. Pitel","orcid":"0000-0002-5138-824X","position":4,"is_corresponding":false},{"id":525252,"name":"Jess F. Peterson","orcid":"0000-0003-2496-8000","position":5,"is_corresponding":false},{"id":261789,"name":"Linda B. Baughn","orcid":"0000-0001-5229-4897","position":6,"is_corresponding":false},{"id":472846,"name":"Kaaren K. Reichard","orcid":"0000-0001-5439-0778","position":7,"is_corresponding":false},{"id":525253,"name":"Rhett P. Ketterling","orcid":"0000-0001-6479-7897","position":8,"is_corresponding":false},{"id":525254,"name":"Sara M. Kloft‐Nelson","orcid":"0009-0005-1301-8706","position":9,"is_corresponding":false},{"id":526263,"name":"Darlene L. Knutson","orcid":null,"position":10,"is_corresponding":false},{"id":525255,"name":"Shakila P. Khan","orcid":"0000-0001-7345-1855","position":11,"is_corresponding":false},{"id":431829,"name":"Naseema Gangat","orcid":"0000-0002-9104-6172","position":12,"is_corresponding":false},{"id":284142,"name":"Mark R. Litzow","orcid":"0000-0002-9816-6302","position":13,"is_corresponding":false},{"id":467811,"name":"William J. Hogan","orcid":"0000-0002-5841-4105","position":14,"is_corresponding":false},{"id":525256,"name":"Alexandra P. Wolanskyj","orcid":"0000-0003-1618-5049","position":15,"is_corresponding":false},{"id":284256,"name":"Aref Al‐Kali","orcid":"0000-0002-0824-3715","position":16,"is_corresponding":false},{"id":472845,"name":"Kebede H. Begna","orcid":"0000-0003-2730-8593","position":17,"is_corresponding":false},{"id":525257,"name":"Michelle A. Elliott","orcid":"0000-0002-7366-9886","position":18,"is_corresponding":false},{"id":525258,"name":"Animesh Pardanani","orcid":"0000-0002-9084-4148","position":19,"is_corresponding":false},{"id":339782,"name":"James M. Foran","orcid":"0000-0003-1673-1708","position":20,"is_corresponding":false},{"id":472847,"name":"Mithun Vinod Shah","orcid":"0000-0002-5359-336X","position":21,"is_corresponding":false},{"id":431828,"name":"Ayalew Tefferi","orcid":"0000-0003-4605-3821","position":22,"is_corresponding":false},{"id":339776,"name":"Hassan B. Alkhateeb","orcid":"0000-0002-3609-8404","position":23,"is_corresponding":false},{"id":525259,"name":"Kevin C. Halling","orcid":"0000-0002-2914-2526","position":24,"is_corresponding":false},{"id":525260,"name":"Vilmarie Rodriguez","orcid":"0000-0003-0990-544X","position":25,"is_corresponding":false},{"id":525261,"name":"Patricia T. Greipp","orcid":"0000-0002-5536-9011","position":26,"is_corresponding":false},{"id":284241,"name":"Mrinal M. Patnaik","orcid":"0000-0001-6998-662X","position":27,"is_corresponding":false},{"id":352728,"name":"Theodora Anagnostou","orcid":"0000-0003-2142-7356","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-18T23:12:57.988348Z","pmid":"31919873","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}