Yafang Wu

Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia

A rare chromosomal translocation, (11;20)(p15;q11), was detected in a 29-year-old male patient diagnosed with acute monocytic leukemia (AMoL) according to the French-American-British classification criteria. Whole chromosome painting analysis with paints for chromosomes 11 and 20 confirmed the result of conventional cytogenetic analysis. Reverse transcriptase polymerase chain reaction revealed the NUP98-TOP1 fusion transcript. To our knowledge, this is the second report of the translocation involving NUP98 and TOP1 genes in AMoL. On reviewing the literature, we suggest that t(11;20)(p15q11) is associated with myelocytic disorders rather than lymphocytic proliferative diseases.

Pulmonary Alveolar Proteinosis as a Terminal Complication in a Case of Myelodysplastic Syndrome with idic(20q

Secondary pulmonary alveolar proteinosis (PAP) is a rare lung disease that has been reported in 13 cases of myelodysplastic syndromes (MDS). A dicentric isochromosome of deleted chromosome 20q, idic(20q–), is a newly recognized rare, but recurrent, cytogenetic anomaly that has been described in 28 cases of MDS. Recently, we encountered an interesting MDS patient with idic(20q–) and secondary PAP. At presentation, she was a 40-year-old woman with pancytopenia and dysplasia involving 2 cell lineages that were compatible with refractory cytopenia with multilineage dysplasia. A chromosome analysis of bone marrow cells using the R-banding technique revealed a karyotype of 46,XX,–20 and +a small metacentric marker chromosome. Fluorescence in situ hybridization demonstrated this marker chromosome to be idic(20q–). Three years after presentation, her disease was complicated by secondary PAP that was confirmed by chest computed tomographic scans and a thoracoscopic lung biopsy, revealing the characteristic periodic acid Schiff stain-positive materials filling the alveoli. The patient subsequently died of respiratory failure 45 months after diagnosis. To our knowledge, this is the first MDS patient with idic(20q–) and secondary PAP to be reported in the literature. Moreover, this patient is also the 29th MDS case with idic(20q–).

Minimally Differentiated Acute Myeloid Leukemia with t(12;22)(p13;q11) Translocation Showing Primary Multidrug Resistance and Expressing Multiple Multidrug-Resistant Proteins

Here we report a rare chromosomal translocation, t(12;22)(p13;q11), which was detected in a 53-year-old female patient diagnosed as having minimally differentiated acute myeloid leukemia (AML-M0) according to the French-American-British classification criteria. Chromosome painting analysis with probes for chromosomes 12 and 22 confirmed the result of the conventional cytogenetic analysis. Reverse transcriptase polymerase chain reaction revealed the TEL-MN1 fusion transcript. Interestingly, she presented primary multidrug resistance and did not respond to several kinds of chemotherapy regimens. Moreover, she could not achieve remission after two doses of monotherapy with Mylotarg. Flow cytometry analysis detected high levels of expression of P-glycoprotein, multidrug-resistant-related protein, lung-related protein, and glutathione S-transferase π in this case at presentation. As far as we know, this is the first report of t(12;22)(p13;q11) translocation involving TEL and MN1 genes in an AML-M0 patient.

Tetraploid clone characterized by two t(15;17) in five cases of acute promyelocytic leukemia.

More than 100 cases of acute myelocytic leukemia (AML) with tetraploidy or near-tetraploidy (NT) have been described in the literature to date [1,2]. These can be divided into primary and secondary NT-AML [3,4]. Primary NT-AML, usually seen in older patients with poor prognosis has chromosomal structural or numerical abnormalities, especially involving chromosomes 5 and 7 [2]. Secondary NT-AML is frequently seen in younger patients than the primary form and has specific chromosomal rearrangements, with a relatively good prognosis in most of them [4]. Among the latter, NT-AML with duplication of t(8;21) is the most common, with 13 cases reported, compared with only 6 cases of NT acute promyelocytic leukemia (APL) with double t(15;17) [5e11]. Here, we report five new cases of NT-APL with double t(15;17) abnormalities and discuss their possible clinical and biological features. From 1998 July to 2008 April, 660 APL patients were examined cytogenetically in our hospital. The NT type with double t(15;17) was detected in 5 of the 660 patients (0.75%). All were men, with a median age of 38 years (range, 21e68). Giant and bizarre blasts were seen on bone marrow smears in all five cases. Chromosome analysis with R-banding of bone marrow cells revealed the karyotype of the abnormal clone to be 92,XXYY,t(15;17)(q22;q21) 2. Fusion of the PML and RARA genes was detected in three cases: in one case by fluorescence in situ hybridization analysis (FISH) using the Vysis LSI PML/RARA dualcolor, dual-fusion probe (Abbott Molecular, Des Plaines, IL) (case 2) and in two cases by reverse transcriptasee polymerase chain reaction (cases 3 and 4). Immunologically, the blasts expressed CD33 in five cases and CD13 in four cases. In addition, CD2 expression was seen in case 2 and CD34 in case 3, respectively. Flow cytometric analysis displayed a tetraploid peak (DNA index Z 1.998) in case 2. All five patients responded well to all-trans retinoic acid (ATRA) alone or a combination of ATRA and arsenic trioxide (As2O3) and remained in complete remission at writing. Acute promyelocytic leukemia is characterized by the translocation t(15;17)(q22;q21), the PMLeRARA fusion gene and a good response to ATRA or As2O3 [12]. Most cases exhibit a diploid karyotype with a single t(15;17).