Insights from a rare myeloproliferative neoplasm with coexisting BCR‐ABL1 fusion gene, CALR, and TET2 mutations treated with nilotinib and ruxolitinib

Abstract

Myeloproliferative neoplasms (MPNs) with concurrent BCR-ABL1 fusion gene and CALR mutation are especially rare. We report a patient with coexisting BCR-ABL1 fusion gene, CALR, and TET2 mutations who was treated with the combination of the second-generation TKI nilotinib and JAK1/JAK2 inhibitor ruxolitinib.

Chronic myeloproliferative neoplasms with concomitant CALR mutation and BCR::ABL1 translocation: diagnostic and therapeutic implications of a rare hybrid disease

“…Including our case, a total of 24 cases with concomitant BCR::ABL1 and CALR mutation have been described so far ( Bonzheim et al, 2015 ; Cabagnols et al, 2015 ; Loghavi et al, 2015 ; Diamond et al, 2016 ; Seghatoleslami et al, 2016 ; Dogliotti et al, 2017 ; Gilles et al, 2017 ; Kandarpa et al, 2017 ; Blouet et al, 2018 ; Boddu et al, 2018 ; De Roeck et al, 2018 ; Klairmont et al, 2018 ; Lewandowski et al, 2018 ; Xia et al, 2019 ; Balducci et al, 2020 ; Da Costa et al, 2020 ; Guidotti et al, 2020 ; Liu et al, 2020 ; Yoon et al, 2020 ; Sobieralski et al, 2022 ; Huo et al, 2023 ).…”

“…In the group with CML preceding Ph-negative MPN (13/24 cases), BM histology at CML presentation in 10/13 cases with available BM data was as follows: CML (CP) histology in 2/10 ( Kandarpa et al, 2017 ; Balducci et al, 2020 ), CML + fibrosis + hybrid MKs including both classical CML MKs with small and hypolobate nuclei and large hyperlobated forms in 3/10 ( Loghavi et al, 2015 ; Gilles et al, 2017 ; Guidotti et al, 2020 ), CML + atypical MKs in 2/10 ( Blouet et al, 2018 ; Da Costa et al, 2020 ), CML + fibrosis in 2/10 ( Diamond et al, 2016 ; Yoon et al, 2020 ), and grade 2 reticulin fibrosis with no other BM data in 1/10 ( Cabagnols et al, 2015 ). In this group, the emergence of the Ph-negative MPN phenotype usually occurred after TKI treatment and CML remission; the histology of BM at Ph-negative MPN emergence was available in 9/13 cases, and it was consistent with either PMF (4/9) ( Loghavi et al, 2015 ; Diamond et al, 2016 ; Kandarpa et al, 2017 ; Huo et al, 2023 ), ET (4/9) ( Dogliotti et al, 2017 ; Blouet et al, 2018 ; Balducci et al, 2020 ; Da Costa et al, 2020 ), or MPN, NOS (1/9) [ 25].…”

“…In the majority of cases with concurrent BCR::ABL1 translocation and CALR mutation, CML was the first diagnosis, followed by Ph-negative MPN (13/24; 54.16%) ( Cabagnols et al, 2015 ; Loghavi et al, 2015 ; Diamond et al, 2016 ; Dogliotti et al, 2017 ; Gilles et al, 2017 ; Kandarpa et al, 2017 ; Blouet et al, 2018 ; Lewandowski et al, 2018 ; Balducci et al, 2020 ; Da Costa et al, 2020 ; Guidotti et al, 2020 ; Yoon et al, 2020 ; Huo et al, 2023 ), and the Ph-negative MPNs were distributed as follows: four myeloproliferative neoplasm not otherwise specified (MPN, NOS); four PMF; and five ET.…”

“…In the group with CML preceding Ph-negative MPN, the clinical manifestations at the second disease occurrence were as follows: high PTL in 9/13 despite good molecular response of CML ( Cabagnols et al, 2015 ; Dogliotti et al, 2017 ; Gilles et al, 2017 ; Lewandowski et al, 2018 ; Balducci et al, 2020 ; Da Costa et al, 2020 ; Guidotti et al, 2020 ; Yoon et al, 2020 ), increasing splenomegaly in 3/13 despite good molecular response of CML ( Diamond et al, 2016 ; Kandarpa et al, 2017 ; Huo et al, 2023 ), anemia in 2/13 despite a good molecular response of CML ( Cabagnols et al, 2015 ; Diamond et al, 2016 ), and appetite loss and fatigue in 1/13 despite a good molecular response of CML ( Huo et al, 2023 ).…”

“…The association of CALR mutations with BCR::ABL1 rearrangement is much rarer, being reported in isolated cases. In this article, we described a case from our daily practice with a long history of CALR -mutated PMF, subsequently developing CML with gaining of BCR::ABL1 rearrangement; meanwhile, through a literature search, we identified 23 cases harboring both CALR mutation and BCR::ABL1 rearrangement ( Bonzheim et al, 2015 ; Cabagnols et al, 2015 ; Loghavi et al, 2015 ; Diamond et al, 2016 ; Seghatoleslami et al, 2016 ; Dogliotti et al, 2017 ; Gilles et al, 2017 ; Kandarpa et al, 2017 ; Blouet et al, 2018 ; Boddu et al, 2018 ; De Roeck et al, 2018 ; Klairmont et al, 2018 ; Lewandowski et al, 2018 ; Xia et al, 2019 ; Balducci et al, 2020 ; Da Costa et al, 2020 ; Guidotti et al, 2020 ; Liu et al, 2020 ; Yoon et al, 2020 ; Sobieralski et al, 2022 ; Huo et al, 2023 ).…”