Mechanical phenotyping of acute promyelocytic leukemia reveals unique biomechanical responses in retinoic acid-resistant populations

Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. Case Report A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. Management & Outcome Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. Discussion This case highlights the importance of monitoring ATRA’s side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

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Acute myeloid leukemia with CPSF6–RARG fusion resembling acute promyelocytic leukemia with extramedullary infiltration

Therapeutic Advances in Hematology ◽

10.1177/2040620720976984 ◽

2021 ◽

Vol 12 ◽

pp. 204062072097698

Author(s):

Xiaoyan Han ◽

Chunxiang Jin ◽

Gaofeng Zheng ◽

Yi Li ◽

Yungui Wang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Retinoic Acid ◽

Acute Promyelocytic Leukemia ◽

Myeloid Leukemia ◽

Retinoic Acid Receptor ◽

Promyelocytic Leukemia ◽

Specific Factor ◽

Acid Receptor ◽

Response To Chemotherapy ◽

Acute Myeloid

Some subtypes of acute myeloid leukemia (AML) share morphologic, immunophenotypic, and clinical features of acute promyelocytic leukemia (APL), but lack a PML–RARA (promyelocytic leukemia–retinoic acid receptor alpha) fusion gene. Instead, they have the retinoic acid receptor beta (RARB) or retinoic acid receptor gamma (RARG) rearranged. Almost all of these AML subtypes exhibit resistance to all-trans retinoic acid (ATRA); undoubtedly, the prognosis is poor. Here, we present an AML patient resembling APL with a novel cleavage and polyadenylation specific factor 6 ( CPSF6) –RARG fusion, showing resistance to ATRA and poor response to chemotherapy with homoharringtonine and cytarabine. Simultaneously, the patient also had extramedullary infiltration.

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