Chronic myeloid leukemia with an e1a3 BCR-ABL fusion protein: transformation to lymphoid blast crisis

Jordi Martinez-Serra,Antonio Gutierrez,Maria A Durán,Juan C Amat,Raquel Del Campo,Joan Besalduch,Jose Luis Antich,Leyre Bento,Teresa Ros,Julio F Iglesias,Magdalena Ginard,Carmen Vidal,Izabela Orlinska

doi:10.1186/2050-7771-2-14

Abstract

Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell. CML is cytogenetically characterized by the presence of the Philadelphia chromosome (Ph’). Most patients with CML express e13a2 or e14a2 mRNAs that result from a rearrangement of the major breakpoint cluster regions (M-BCR) generating the 210-kDa (p210BCR-ABL) fusion proteins b2a2 or b3a2 respectively. The e1a3 CML-related atypical translocation has been reported with an indolent clinical course, low leukocyte count, long chronic phase even without treatment and good response to therapy. We report the case of a patient initially diagnosed as CML in chronic phase whose cells expressed the e1a3 variant. The patient readily responded to imatinib 400 mg with the achievement of a rapid complete cytogenetic response and the normalization of the blood count values, but after 5 months transformed into lymphoid blast crisis.

Highlights

Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell. This leukemia is cytogenetically characterized by the presence of the Philadelphia chromosome (Ph’), which results from the reciprocal translocation t(9;22) (q34; q11) that juxtaposes the c-abl oncogene 1 (ABL1) gene on chromosome 9 with the breakpoint cluster region (BCR) gene on chromosome 22 generating the BCRABL1 oncogene [1,2,3]
The e1a3 BCR-ABL1 related CML has been reported with an indolent clinical course, low leukocyte count, long chronic phase even without treatment and good response to therapy [9,10]
Due to the reduced number of e1a3 CML cases, it is necessary to accumulate more clinical evidences in order to clarify the relationship between the presence of the e1a3 BCR-ABL translocation and their clinical course that could be similar or worse than standard p210 CML as it could confer a higher risk of transformation to acute lymphoblastic leukemia (ALL)

Summary

Background

Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell. Most patients with CML express e13a2 or e14a2 mRNAs that result from a rearrangement of the major breakpoint cluster regions (M-BCR) generating the 210-kDa (p210BCR-ABL) fusion proteins b2a2 or b3a2 respectively, mainly associated to CML. We report the case of a patient initially diagnosed as CML in chronic phase whose cells expressed the e1a3 variant This patient readily responded to imatinib 400 mg with the achievement of a rapid complete cytogenetic response and the normalization of the blood count values, but after 5 months transformed into lymphoid blast crisis. A fresh sample from the bone marrow aspirate was collected for cytogenetic and FISH analysis They revealed the presence of a karyotype 46XY, t(9;22) (q34;q11.2) that confirmed the diagnosis of CML in chronic phase. The rest of myeloid and T-cell studied markers expression were negative (Figure 2)

Findings

Discussion

Conclusion