Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu, Korea.
Particularly, the der(1;18)(q10;q10) translocation is very rare in hematologic malignancies. Only 3 cases of hematologic malignancy with der(1;18)(q10;q10) translocations have been reported since the translocation was first described by Wan et al.; each was a case of refractory anemia with excess blasts (RAEB), myeloproliferative disorder (MPD), and essential thrombocythemia (ET) [2, 3]. A few other cases including non-Hodgkin's lymphoma (NHL), polycythemia vera, and primary myelofibrosis had der(1;18) (q10;q10) translocations as a part of a more complex karyotype, but lacked detailed case descriptions [1, 4, 5, 6].
Three years ago, a 73-year-old woman was admitted to our hospital because of pancytopenia. Her complete blood cell count (CBC) showed a hemoglobin (Hb) level of 7.7 g/dL with a mean corpuscular volume (MCV) of 105 fL (reference, 80-99 fL), a platelet count of 58×109/L, and a white blood cell (WBC) count of 2.29×109/L with 40% segmented neutrophils, 46% lymphocytes, 8% monocytes, and 3.9% eosinophils. The peripheral blood smear showed macrocytic erythrocytes without immature cells. At that time, a bone marrow (BM) biopsy was not performed. Theserum vitamin B12 level was 234 pg/mL (reference, 211-911 pg/mL) and the folate level was >20 ng/mL (reference, 4.2-19.9 ng/mL). Despite vitamin supplementation therapy for 3 years, her pancytopenia did not improve. However, her general health status was sustained at a tolerable state. Three months ago, the patient was diagnosed as having gastric adenocarcinoma and underwent a total gastrectomy. At that time, her CBC still showed pancytopenia with the following blood markers: Hb, 9.1 g/dL; WBC, 2.04×109/L (47.6% segmented neutrophils, 40.8% lymphocytes, 6.5% monocytes, and 1.3% eosinophils), and platelets, 58×109/L. The MCV was 102 fL and the serum vitamin B12 level was 1,180 pg/mL. The serum iron, total iron binding capacity, and ferritin levels were 114.1 µg/dL (reference, 29-164 µg/dL), 301 µg/dL (reference, 22-433 µg/dL) and 532.7 ng/mL (reference, 10-291 ng/mL), respectively. The reticulocyte level was 1.83% (reference, 0.5%-1.5%). The BM was hypocellular with 38.6% myeloid cells, 37.0% erythroid cells, and 20.7% lymphocytes. The erythroid series were slightly increased and a mild dyserythropoiesis (megaloblastic changes, binuclarity, and nuclear buddings) was observed (Fig. 1A). Myeloid cells and megakaryocytes were unremarkable in morphology and number. BM iron was sufficient (3+/5+). A BM cytogenetic study revealed the following chromosome abnormalities: 46,XX,+1,der(1;18)(q10;q10)/46,XX (Fig. 1B). As a result of the BM findings and the clonal chromosomal changes, the patient was diagnosed as having unclassifiable myelodysplastic syndrome (MDS-U), according to World Health Organization classification system. Because of her old age and stable general condition, the patient is only receiving vitamin supplementation therapy and is scheduled forregular follow-up visits.
Although a der(1;18)(q10;q10) translocation has been reported in a case of NHL, this translocationis mainly observed in myeloid disorders, primarily in myeloproliferative neoplasms. Moreover, 3 cases including our case had the der(1;18)(q10;q10) translocation as the sole abnormality; this indicates that der(1;18)(q10;q10) might be a primary change in myeloid diseases.
With unbalanced der(1;18)(q10;q10) translocations, either trisomy 1q or monosomy 18p has been suggested to contribute to leukemogenesis. Trisomy 1q may contribute to leukemogenesis through a gene dosage effect as the region q25-q32 has been suggested to give rise to a proliferation advantage of the neoplastic clone in hematologic malignancies . Monosomy 18p may also contribute to clonal proliferation due to the loss of putative tumor suppressor genes. Recently, the l(3)mbt-like 4 (
The prognostic effect of an extra 1q chromosome in myeloid disorders has been variable. While the presence of the der(1;7)(q10;p10) translocation was reported to correlate with leukemic transformation and poor prognosis in MDS [9,10], the der(Y)t(Y;1)(q12;q12) translocation does not lead to a poor prognosis . For cases harboring a der(1;18) (q10;q10) translocation, the prognostic implications were also variable (Table 1). The MPD case showed a very stable clinical course for 2 years . Similarly, the ET case also showed a relatively stable treatment progress. However, the RAEB case displayed an aggressive clinical course and the patient died just 1 month after the initial presentation . In contrast, our case showed a very indolent clinical course. Although our case was diagnosed as having MDS-U just a few months ago, there is a distinct possibility that this patient already had MDS 3 years ago, based on the persistent pancytopenia. This supposition sufficiently supports the indolent progression of the MDS-U with the der(1;18)(q10;q10) translocation.
In conclusion, we report a rare case of MDS-U with a der(1;18)(q10;q10) translocation showing a very indolent clinical progress. Although all but one of the previous cases showed a mild clinical presentation, the prognostic implications of the der(1;18)(q10;q10) translocation cannot be extrapolated at this point due to the very small number of cases. Therefore, the prognostic significance as well as phenotypic variance of the der(1;18)(q10;q10) translocation have to be determined through the collection and analysis of further cases.