Background The BCR-ABL1 fusion gene underlying the pathogenesis of CML can arise from a variety of breakpoints. The e13a2 and e14a2 transcripts formed by breakpoints occurring around exon 13 and exon 14 of the BCR gene respectively are the most common. Methods We undertook a retrospective audit using local laboratory database and electronic patient care records of 69 CML patients with an e13a2 or e14a2 transcript type identified in our regional population. Results The e13a2 group was on average significantly younger (45.0 years v 54.5 years), had a higher average white cell count (189.8 × 10 9 /l v 92.40 × 10 9 /l) and lower platelet count (308 × 10 9 /l v 644 × 10 9 /l) in comparison to the e14a2 group suggesting that these are distinct biological entities. Over an average follow-up of 33.8 months and 27.2 months for the e13a2 and e14a2 groups we observed an inferior molecular response to imatinib in the e13a2 group. A significantly lower number of patients in the e13a2 arm met European Leukemia Net criteria for optimal response at 12 months therapy (17.64% v 50.0%) and were slower to obtain deep molecular responses MR 4 or MR 4.5 . Conclusion Patients with an e13a2 transcript demonstrate an inferior molecular response to imatinib in our regional population.

Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.

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<b>Hintergrund:</b> Das BCR-ABL1-Fusionsgen, das der Pathogenese der CML zugrunde liegt, kann aus einer Reihe verschiedener Bruchstellen entstehen. Die häufigsten Varianten sind die Transkripte e13a2 und e14a2, die durch Bruchstellen im Bereich von Exon 13 bzw. Exon 14 des BCR-Gens entstehen. <b>Methoden:</b> In einer retrospektiven Analyse werteten wir lokale Labordatenbanken und elektronische Patientenakten von 69 CML-Patienten mit e13a2- oder e14a2-Transkriptvariante aus, die wir in unserer regionalen Population identifiziert hatten. <b>Ergebnisse:</b> Die e13a2-Gruppe war im Durchschnitt signifikant jünger (45,0&#x2009;Jahre vs. 54,5 Jahre), ihre durchschnittliche Leukozytenzahl war höher (189,8 × 10⁹/l vs. 92,40 × 10⁹/l) und die Thrombozytenzahl niedriger (308 × 10⁹/l vs. 644 × 10⁹/l) als in der e14a2-Gruppe, was darauf hindeutet, dass es sich um unterschiedliche biologische Entitäten handelt. Über einen durchschnittlichen Nachbeobachtungszeitraum von 33,8 Monaten (e13a2) bzw. 27,2 Monaten&#x2009;(e14a2) beobachteten wir ein schlechteres molekulares Ansprechen auf Imatinib in der e13a2-Gruppe. Eine signifikant geringere Anzahl von Patienten im e13a2-Arm erfüllte die Kriterien des European Leukemia Net für ein optimales Ansprechen nach 12-monatiger Therapiedauer (17,64% vs. 50,0%), und es dauerte länger, bis sie ein umfassendes molekulares Ansprechen (MR⁴ oder MR^4.5) erreichten. <b>Schlussfolgerung:</b> In den Populationen unserer Region zeigen Patienten mit einer e13a2-Transkriptvariante ein schlechteres molekulares Ansprechen auf Imatinib.