PMC6079565_01
Chronic myeloid leukemia - blast crisis characterization (A) Increased promyelocytes seen in bone marrow aspirate using hematoxylin and eosin (H&E) staining; photographed at 1000x magnification (B) Conventional cytogenetics demonstrated an abnormal karyotype - 46, XY, t(9;22)(q34;11.2), t(15;17)(q24;q21). Fluorescent in situ hybridization (FISH) confirmed the presence of (C) t(9;22)(q34;q11.2)/BCR-ABL, and (D) t(15;17)(q24;q21)/PML-RARA fusions.
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Bone marrow biopsy and aspirate revealed 80% cellularity, 88% promyelocytes, 2% blasts, and was notable for replacement of normal marrow elements with sheets of promyelocytes (Fig. 1a). Unstimulated peripheral blood culture revealed a male karyotype with a reciprocal translocation between the long arms of chromosomes 9 and 22-t(9;22)(q34;q11.2) and a reciprocal translocation between the long arms of chromosomes 15 and 17-t(15;17)(q24;q21) in all cells analyzed (Fig. 1b). PML-RAR fusions, which detect the t(15;17)(q24;q21.1) were observed in 168 of 200 interphase nuclei scored by FISH analysis (Fig. 1c and d respectively).
Laboratory parameters of our patient demonstrating response of promyelocytic blast crisis to dual targeted therapy (A) Markers of disseminated intravascular coagulation (DIC) - fibrinogen and D-dimer - improved with ATRA-ATO therapy and normalized by day 5, (B) Peripheral blood myeloblast and promyelocte fractions of total white blood cell (WBC) count decreased gradually and were completely eliminated by day 16, and (C) PML-RARA and BCR-ABL transcript levels, assessed using quantitative real time polymerase chain reaction (qRT-PCR), decreased and demonstrated efficacy of ATRA-ATO therapy.
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During the first week of treatment, the blasts and promyelocytes gradually decreased and laboratory measures of disseminated intravascular coagulation (DIC) including D-dimer, fibrinogen, fibrin split products, and fibrin monomers trended towards normal (Fig. 2a and b). Molecular analysis revealed reduced BCR-ABL p210 and PML-RARA transcript levels to 17.225 IS-NCN and 1.28 IS-NCN respectively (Fig. 2c).