Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance

Abstract

The most common BCR-ABL transcripts in chronic myeloid leukemia (CML) are e13a2(b2a2) and e14a2(b3a2). Other transcripts such as e1a2 are rare and their outcome with tyrosine kinase inhibitors (TKI) therapy is undefined. We analyzed 1292 CML patients and identified 14 with only e1a2 transcripts, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Of the CP, 4 achieved complete hematologic response (CHR); 2, complete cytogenetic response (CCyR); 2, partial cytogenetic response (PCyR), and 1 did not respond to imatinib. Five patients progressed to myeloid BP (3), lymphoid BP (1), or AP (1). The AP patient received various TKIs sequentially and achieved only CHR. BP patients received hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone) plus imatinib/dasatinib or idarubicin plus cytarabine (Ara-C); 2 did not respond, 1 had CCyR, and 1 short-lasting complete molecular response (CMR). Overall, cytogenetic responses lasted 3 to 18 months; only 2 achieved major molecular response (MMR) on TKI. P190BCR-ABL CML is rare and is associated with an inferior outcome to therapy with TKI. These patients need to be identified as high-risk patients.

Frequency of Bcr-Abl Fusion Oncogene Splice Variants Associated with Chronic Myeloid Leukemia (CML)

“…De-Lemos et al [24] reported that statistically significant difference was found for the levels of expression of transcripts b2a2 and b3a2 at six months of imatinib treatment, which shows that b2a2 may have a better molecular response than b3a2. Verma et al [25] reported that rare variants like e1a2 have an inferior response to imatinib. Sharma et al [26] found that 59% patients with b2a2 type achieved complete cytogenetic response (CGR) as compared to 28% patients with b3a2 (p = 0.04) while in 24 patients with minor or no CGR, 25% had b2a2 compared to 75% b3a2 type (p = 0.04).…”

Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors

“…13,33 More than 95% of patients with CML have e13a2 (b2a2), e14a2 (b3a2), or both transcripts coding for p210 BCR-ABL1 tyrosine kinase, whereas only a minority express rare variants such as e1a2 transcripts, 34 which code for p190 BCR-ABL1, which is associated with rapid disease progression. Previous reports have suggested that patients with e14a2 achieve deeper molecular response to standard dose imatinib 23 and have higher platelet counts compared with patients with e13a2 transcripts.…”

How I treat CML blast crisis

“…A score of Ͼ 87 indicates high risk.] 102 In addition, distinct markers such as major route ACA, 15 p190 BCR-ABL , 103 and signs of acceleration may be suitable for early prediction of progression (Table 4). In addition, BMI1 and CIP2A levels at diagnosis have been reported predictive of BC.…”