Coincidence of Gaucher's disease due to a private mutation and Ph′ positive chronic myeloid leukemia

Abstract

We report the case of a 46-year-old female with coexisting type I Gaucher's disease and chronic myeloid leukemia (CML). The diagnosis of Gaucher's disease was made in early childhood by bone marrow biopsy and was recently confirmed by biochemical demonstration of reduced leukocyte beta-glucocerebrosidase activity and the presence of Gaucher cells in a bone marrow aspirate. We analyzed the patient's genomic DNA for the underlying glucocerebrosidase mutations and have found homozygosity for a C-->T transition in cDNA nucleotide 593 (159 Pro-->Leu), presently an undescribed mutation. After initiation of replacement therapy with alglucerase we observed a significant increase of the platelet count in our patient. The diagnosis of CML was based on standard hematological parameters and the detection of the Philadelphia chromosome (Ph). With intermittent treatment with busulfan the patient has remained in chronic phase for nine years. The patient suffered from hepatosplenomegaly and thrombocytopenia, both of which can be caused by Gaucher's disease and CML. The aggravation of skeletal manifestations of Gaucher's disease, which occurred at the time of diagnosis of CML, could be due to increased production of leukocyte-derived glucocerebrosides that were not appropriately degraded because of the genetic beta-glucocerebrosidase deficiency.

Gaucher disease and chronic myeloid leukemia: first reported patient receiving enzyme replacement and tyrosine kinase inhibitor therapies simultaneously

“…Furthermore, the report from the international collaborative Gaucher group registry (ICGGR) has also reported an increased risk for multiple myeloma (RR = 5.9) but not for overall cancer (RR = 0.79) [24]. The interest on myeloid malignancies incidence of Gaucher disease patients has generated few case reports in PubMed [19,23], and only two described a CML case, one in 1982, previous to the availability of ERT and TKI in a patient who progress to blastic crisis [16], the second case was published in 1998 from a non-Ashkenazy patient diagnosed of CML in 1988, after diagnosis, the patient started busulfan therapy for CML, but an increase on bone symptoms was recorded and due to the availability of ERT the patient started ERT with good outcomes [17]; in both reports, the increased turnover rate of leukocytes increased the accumulation of GC, the number of Gaucher's/ pseudo-Gaucher cells, and a worsening on GD symptoms. In the case here presented, a key classical diagnostic feature of CML was founded during the initial assessment, the presence of pseudo-Gaucher cells.…”

“…There are only two CML cases reported on GD1 population in PubMed (accessed 04 January 2018), both of them occurred previous to the imatinib era [16,17]. Here, the first case of a chronic phase CML diagnosis in a patient with GD1 who receive both ERT and TKI therapy is presented with the aim to provide new information regarding safety and management issues when both conditions require simultaneously therapy.…”

Gaucher Disease and Cancer: Concept and Controversy

“…Associated cancers include multiple myeloma (Table 1, [15–30]), chronic lymphocytic leukemia [31–34], chronic myeloid leukemia [35, 36], acute leukemia [37–39], large B-cell lymphoma [40], T-cell lymphoma [41], Hodgkin's disease [42–44], glioblastoma multiforme [45], lung cancer [46, 47], dysgerminoma [48], hepatocellular carcinoma [49, 50], and bone cancer [51–54]. Of the aforementioned malignancies, multiple myeloma has been most frequently reported (Table 1).…”