MPAL has no specific chromosomal abnormalities. Owaidah et al. demonstrate that 68% of MPAL patients have clonal abnormalities, among which KMT2A translocation is the most common, followed by BCR-ABL.(5, 6) KMT2A rearrangement is more frequent in pediatric MPAL (especially infants), while BCR-ABL is more frequent in adults.(7) The case described herein is interesting because PML-RARα rearrangement complicated with t(15;17) in MPAL T/M cases is extremely uncommon. In general, PML-RARα fusion and t(15;17) are regarded as highly specific for acute promyelocytic leukemia (APL). There is few cases of AML with PML-RARα fusion and t(15;17) that were neither immunophenotypically nor morphologically consistent with APL.(8) To sum up, MPAL T/myeloid (M5) with PML-RARα positivity and t(15;17) is indeed quite rare.
The immunophenotype supported the diagnosis of MPAL T/M. In addition, we concerned that CD7 and CD34 were highly expressed in this case. CD7 is considered to be one of the T lymphoid-associated antigens, but it is not as specific as CD3. AML with CD7 high expression is generally connected with poor prognosis.(9, 10) Expression of CD34 also predicted unsatisfactory outcome. Furthermore, some researchers demonstrated that the positive rate of CD34 in MPAL was as high as 84%.(11–14) However, individual case report cannot verify these conclusions. The stratification of MPAL risk level needs more cases series and analytical studies to develop.
FLT3 is one of the most common mutations in AML, whose occurrence is often associated with poor prognosis. (15, 16)However, due to the rarity of MPAL, there are few studies on FLT3 mutation in MPAL. Zhang et al. indicated that ITD mutation was the dominant FLT3 mutation in MPAL patients. (17)Mutation in FLT3-ITD was also detected in this case. Some researchers believed that stem cell transplantation was more beneficial than chemotherapy for AML patients with FLT3-ITD mutation.(18) However, whether that applies to MPAL patients is worth further study.
MPAL is characterized by unique clinical and biological characteristics, with higher incidence in adults than in children, which is generally associated with worse prognosis.(4) There may be several reasons for the poor prognosis. First, the leukemia stem cells of MPAL are primitive pluripotent progenitors, which replicate too slowly to be resistant to chemotherapy. Second, due to the transformable phenotype, MPAL cells are capable to adapt to therapy. Third, a part of MPAL can highly express resistance-conferring P-glycoprotein.(19, 20) Therefore, the choice of chemotherapy regimen has always been a major difficulty in MPAL treatment. Gerr H, Rubnitz JE and their coworkers indicated that ALL-directed chemotherapy usually showed better outcome than AML-directed therapies in children. If the initial chemotherapy regimen was not effective, the conversion regimen could be chosen (from ALL-directed switch to AML-directed or vice versa). More than half of patients were able to achieve CR in the second regimen.(21, 22) Nevertheless, some researchers revealed that combined AML/ALL type regimens were more effective than single regimen for adult patients. The CR rate of combined chemotherapy was the highest (71%), followed by ALL-directed (64%), and the lowest was AML-directed (33%).(23) Moreover, Zhang and his coworkers demonstrated that combined-type regimens or ALL-based protocols are effective for the treatment of adult MPAL.(14) As such, we managed the patient with combined chemotherapy for ALL and AML, which contributed to his achievement of CR.
In conclusion, we reported a pretty unfrequent case of MPAL T/M with PML/RARα rearrangement and t(15;17). The outcome of this patient was markedly satisfactory with combined AML/ALL type regimens (DA + VP) and ATRA as well.