Concurrent chronic myeloid leukemia and CALR-mutated myeloproliferative neoplasm.



After the JAK2 V617F mutation, insertion and/or deletion (indel) mutations of CALR exon 9 are the second most common driver mutations in the myeloproliferative neoplasms (MPN) of essential thrombocythemia and primary myelofibrosis and their detection is considered a major diagnostic criterion for these malignancies. It is becoming increasingly apparent that MPNs harboring CALR mutations (along with the mutations of JAK2 V617F and MPL exon 10) may occur in patients with BCR-ABL1-positive chronic myeloid leukemia (CML) as evidenced by a wave of recently reported cases. The CALR-positive MPN and CML may appear concurrently with composite morphology or sequentially with either malignancy revealed as a consequence of specific treatment for one of the malignancies (Table 1(Tab. 1); References in Table 1: Balducci et al., 2019[1]; Blouet et al., 2018[2]; Boddu et al., 2018[3]; Bonzheim et al., 2015[4]; Cabagnols et al., 2015[5]; da Costa et al., 2019[6]; De Roeck et al., 2018[7]; Diamond et al., 2016[8]; Dogliotti et al., 2017[9]; Gilles et al., 2015[10]; Guidotti et al., 2020[11]; Jeromin et al., 2017[12]; Kandarpa et al., 2017[13]; Klairmont et al., 2018[14]; Lewandowski et al, 2018[15]; Loghavi et al., 2015[16]; Nomani et al., 2016[18]; Pagoni et al., 2014[19]; Seghatoleslami et al, 2016[20]; Xia et al., 2019[21]). Review of patients shows that the presenting malignancy was unknown in one case, CML in 11/24 (46 %) and CALR-mutated MPN in the remaining 12/24 (50 %) cases. Evidence exists for molecular abnormalities occurring within a single clone and in distinct clonal populations.

Table 1

Clinical presentation order of cases of co-existing BCR-ABL1-positive chronic myeloid leukemia (CML) and CALR-positive myeloproliferative neoplasm (MPN). ET: essential thrombocythemia; PMF: primary myelofibrosis; MF: myelofibrosis; UNK: unknown

While co-existence of CML and another MPN has clinical relevance with respect to selection and timing of tyrosine kinase inhibitor therapy, there is currently insufficient follow-up data to ascertain overall survival of such cases. There is limited value in assessing the JAK2 V617F mutation in all newly presenting CML cases (McCarron et al., 2012[17]): screening for the less frequent CALR and MPL mutations in all likelihood would show a similar redundancy. Given the low incidence but increasing awareness of co-existing CML and MPN, testing for the relevant rearrangement should therefore be implemented when there is clinical, hematological or morphological evidence.

Conflict of interest

The author declares no conflicts of interest.