ZBTB16-RARα-Positive Atypical Promyelocytic Leukemia: A Case Report
Laura Pardo Gambarte1, Aída Franganillo Suárez1, Javier Cornago Navascués1,2
1Department of Hematology, Fundación Jiménez Díaz University Hospital, 28040 Madrid, Spain.
Background:
The majority of patients with acute promyelocytic leukemia (APL) manifest a specific chromosomal translocation t(15;17)(q22;q21), characterized by the fusion of RARA and PML genes. However, a proportion of APL cases are due to variant translocations, being t(11;17) (q23;q21) the most common amongst them. With the major exception of ZBTB16-RARA t(11;17) APL, these variant APL cases present similar morphological features as classic APL and are characterized by a lack of differentiation response to retinoids.
Case Summary:
We describe the case of variant APL with the ZBTB16-RARA fusion gene, showing a distinct morphology of classical APL, characterized by crystalline intracytoplasmic inclusions in both peripheral blood (PB) and bone marrow (BM) patients' blasts. Our patient was treated with two courses of intensive chemotherapy, initiating maintenance treatment with all-trans retinoic acid (ATRA) on day twenty-eight of the second course. Our patient achieved complete remission (CR) once the intensive chemotherapy was combined with ATRA.
Conclusions:
This is the second case described of APL with t(11;17) that showed crystalline intracytoplasmic inclusions. The finding of these morphological features may suggest the presence of a variant translocation with RARA, being that both cases described are related to the presence of t(11;17). Despite induction treatment with intensive chemotherapy that included a seven-day continuous treatment with cytarabine (200 mg/m2), plus daily idarubicin (12 mg/m2) during the first three days, our patient did not achieve complete remission (CR) until scheduled 3 + 7 regimen combined with ATRA treatment was established. This observation suggests that ATRA may be partially effective in some ZBTB16-RARA APLs.
Insights
Variant acute promyelocytic leukemia (APL) with ZBTB16-RARA translocation, though rare, can present with crystalline inclusions. Combination chemotherapy and all-trans retinoic acid (ATRA) achieved complete remission in a patient with this APL subtype.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Acute promyelocytic leukemia (APL) typically involves the t(15;17) translocation, fusing RARA and PML genes.
- Variant translocations, such as t(11;17), account for a subset of APL cases.
- Most variant APLs, except for ZBTB16-RARA, do not respond to retinoids and share morphology with classic APL.
Observation:
- A case of variant APL with the ZBTB16-RARA fusion gene presented with crystalline intracytoplasmic inclusions in peripheral blood and bone marrow blasts.
- This morphology is characteristic of classic APL, making diagnosis challenging.
- The patient underwent two courses of intensive chemotherapy followed by all-trans retinoic acid (ATRA) maintenance.
Findings:
- The patient achieved complete remission (CR) only after intensive chemotherapy was combined with ATRA.
- This is the second reported case of t(11;17) APL exhibiting crystalline intracytoplasmic inclusions.
- Standard induction chemotherapy alone did not induce CR, highlighting the importance of ATRA in this specific APL variant.
Implications:
- The presence of crystalline intracytoplasmic inclusions may indicate a variant RARA translocation, specifically t(11;17).
- ATRA may have partial efficacy in treating ZBTB16-RARA APL, challenging the general understanding of retinoid resistance in variant APLs.
- Further research is warranted to explore the therapeutic potential of ATRA in similar APL cases.
