|Year : 2015 | Volume
| Issue : 4 | Page : 914-916
Transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia as progression of myeloid neoplasm with platelet-derived growth factor ß rearrangement
Xue Shi, Zhan Su, Chunting Zhao, Xianqi Feng
Department of Haematology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
|Date of Web Publication||15-Feb-2016|
Department of Haematology, The Affiliated Hospital of Qingdao University, Qingdao 266003
Source of Support: None, Conflict of Interest: None
Myeloid neoplasms associated with platelet-derived growth factor b (PDGFRB) rearrangement usually keep only one morphologic type unless blast crisis. We describe a unique case of hematological features transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia, and imatinib showed no clinical therapeutic effects. The phenomenon indicates that different types of myeloid neoplasms associated with PDGFRB rearrangement can transform into one another with the progression of the disease, and to some extent, this transformation suggests the aggravation of disease.
Keywords: Morphology, myeloid neoplasm, platelet-derived growth factor b, transformation
|How to cite this article:|
Shi X, Su Z, Zhao C, Feng X. Transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia as progression of myeloid neoplasm with platelet-derived growth factor ß rearrangement. J Can Res Ther 2015;11:914-6
|How to cite this URL:|
Shi X, Su Z, Zhao C, Feng X. Transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia as progression of myeloid neoplasm with platelet-derived growth factor ß rearrangement. J Can Res Ther [serial online] 2015 [cited 2022 Nov 26];11:914-6. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/914/160922
| > Introduction|| |
In recent years, the rearrangements of platelet-derived growth factor β (PDGFRB) gene at chromosome band 5q33 were recognized in some myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes/MPNs (MDS/MPN) cases.  Acute leukemias, even concurrent acute myeloid leukemia, and T lymphoblastic lymphoma were also founded.  These patients had a very good response to the treatment of tyrosine kinase inhibitor. Therefore, WHO 2008 classification singled these diseases out and defined them as myeloid neoplasms associated with PDGFRB rearrangement. Usually, these entities keep only one sort of cell morphology type ahead of blast crisis. Here, we report a rare case transforming from atypical chronic myeloid leukemia (aCML) to chronic myelomonocytic leukemia (CMML), and to our knowledge, there's no literature exhibited at present.
| > Case report|| |
A 37-year-old man was admitted to hospital presenting with the symptom of abdominal distension for 3 months in May 2010, and because of aggravating for 2 months in July 2012 successively.
The first admission
Physical examination revealed mild splenomegaly. Blood count showed white blood cell (WBC) 150 × 109/L, hemoglobin (Hb) 127 g/L, platelet (PLT) 192 × 109/L. The blood film showed blasts 0%, myelocytes 4%, metagranulocytes 18%, stab cells 20%, segmented neutrocyte 46%, lymphocyte 10% and monocyte 0%. Bone marrow aspirate smear showed hypercellularity with prominent granulocyte proliferation, in which myeloblasts took up of 0%, progranulocytes 0.5%, myelocytes 9%, metagranuiocytes 20.5%, stab cells 23%, and segmented neutrocyte 32%, and monocyte 0% [Figure 1]. Immunophenotype displayed CD33 87.3% and negative for CD14. G-banded analysis revealed the karyotype of 46, XY, t(5;12)(q33;p13), without Philadelphia chromosome. Bcr/abl fusion gene detected the negative by molecular genetic analysis. Fluorescence in situ hybridization detection found the ets variant 6 (ETV6)/PDGFRB rearrangement. According to the WHO classification, a diagnosis of myeloid neoplasm associated with PDGFRB rearrangement (with hematological features of aCML) was made. The patient was treated with hydroxyurea, and maintained WBC < 10 × 109/L, with normal Hb and PLT count. One year later, the patient stopped hydroxyurea himself.
|Figure 1: Bone marrow aspirate smear of a 37-year-old man at first admission, which showed atypical chronic myeloid leukemia characteristic|
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The second admission
The patient exhibited pale skin with ecchymosis all over the body, and spleen was palpated 15 cm inferior to the rib margin. Blood count revealed WBC 67.76 × 109/L, Hb 38 g/L, PLT 14 × 109/L. The blood film showed myeloblasts 3%, progranulocytes 12%, and promonocyte 13%, monocyte 32%. Bone marrow aspirate smear showed myeloblasts accounted for 4%, progranulocytes 4%, myelocytes 15%, erythron 13.5% with dysplastic changes, and promonocyte 11.5%, monocyte 11% [Figure 2]. Immunophenotype displayed CD14 92.4% and CD33 98.6%. The karyotype was 46, XY, t(5;12)(q33;p13), add(22)(q13). PDGFRβ rearrangement still existed without BCR/ABL1 fusion, and sequencing analysis detected no mutation. The diagnosis was myeloid neoplasm associated with PDGFRβ rearrangement (with hematological features of CMML), then he accepted imatinib treatment. The WBC count could be slightly reduced and kept at around 20-40 un109/L although the drug had no effect on Hb or PLT count, and then he died from cerebral hemorrhage 5 months later. There was no sign of blast crisis in this period.
|Figure 2: Bone marrow aspirate appeared to transform to chronic myelomonocytic leukemia at the patient's second admission 2 years later|
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| > Discussion|| |
To date, more than 20 fusion genes involving PDGFRB have been founded, and ETV6 is the most common partner. In WHO 2008 classification, diseases with such features are lumped together into a category just as that of platelet-derived growth factor receptor α (PDGFRA) and fibroblast growth factor receptor 1, and it's emphasized that a final diagnosis should include the histomorphological and clinical criteria.  These neoplasms usually keep only one morphologic type during the course of the disease unless blast crisis. The hematological features of our case transformed from aCML to CMML shortly before his death, and to our knowledge there was no report about such phenomenon. Similarly, only one case with PDGFRA mutation was observed experiencing morphology transformation. 
Whereas it is interesting that monocytic proliferation might occur when cases of MDS switch into MDS/MPN, and to some extent, this transformation suggested the aggravation of disease. Breccia et al.  found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB), but later on (range 2-8 months) developed into CMML. Wang et al.  identified 120 CMML cases, of which 20 cases (16.7%) had a previous diagnosis of MDS, and the median time to evolution from MDS to CMML was 29 months. At last, three cases (17%) transformed to acute myeloid leukemia. Singh et al.  reported 3 cases of MDS-RAEB transforming into CMML in 7-15 months, in which one of them progressed to acute myelomonocytic leukemia with a novel translocation t(5;12)(p13;q24). However, whether MDS/MPN is the natural outcome of MDS, or whether it tends to transformation when it has some characteristics initially, for example, monocytosis, , having rare chromosome disorders needs to be further confirmed.
Genetically, almost 80% of aCML cases have clonal chromosome abnormalities,  in which PDGFRA and PDGFRB gene rearrangement can be found. Clonal chromosome abnormalities are found in 20-40% of CMML cases, which usually have a shorter survival time compared to cytogenetically normal CMML patients. 1-2% of CMML patients have a rare t(5;12)(q33;p13) chromosome translocation.  Sometimes, novel chromosomal aberrations can be detected at the time of transformation between different subtypes of MDS/MPN, or transformation from MDS to MDS/MPN, or progression to AML. Klampfl et al.  investigated chromosomal aberrations in MPN cases and found changes of chromosomes 1q, 7q, 5q, 6p, 7p, 19q, 22q, and 3q were positively associated with post-MPN acute myeloid leukemia. Our case exhibited solo chromosomal aberrations associated with PDGFRB rearrangement when the disease came on, then additional chromosome 22q+ appeared at the time of disease progression. In general, neoplasms with PDGFRB rearrangement show a response to imatinib, but our patient exhibited almost no response and died only 5 months later even during the course of therapy of imatinib. Comparing our case to that of CMML without PDGFRB mutation, we should not ignore the effect of additional chromosome 22q+, and perhaps other potential genetic aberrations, to the drug resistance. So if a patient presents novel chromosomal aberrations, even if without cytogenetics change, we should pay attention to the transformation or progression of the disease. It's necessary to intensify morphology and genetics monitoring, even to modulate therapy.
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[Figure 1], [Figure 2]