ASXL1 mutations in AML are associated with specific clinical and cytogenetic characteristics.

Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.

Rituximab and lenalidomide combination treatment for rheumatoid arthritis complicated with myelodysplastic syndrome: A case report.

Rheumatoid arthritis patients might experience several hematologic complications. The development of myelodysplastic syndrome is not clearly associated with RA, even though it has been described in some patients with pre-existing disease. There are only few data available in the literature concerning the therapeutic approach of such patients. Herein, we report a case of RA complicated with progressive MDS, successfully treated with rituximab and lenalidomide combination therapy.

Cryptogenic organizing pneumonia in Sweet's syndrome: case report and review of the literature.

BACKGROUND AND AIMS: Sweet's syndrome or acute febrile neutrophilic dermatosis is characterized by fever, leukocytosis and tender erythematous plaques, which show infiltration by mature neutrophils on histological examination. Pulmonary involvement is rare in Sweet's syndrome. METHOD: We describe the case of a 17-year-old man with a myelodysplastic syndrome following therapy for Hodgkin's lymphoma who developed Sweet's syndrome and cryptogenic organizing pneumonia. In addition, we conducted a review of the related English literature. RESULTS: Literature review yielded six similar reports of biopsy-proven cryptogenic organizing pneumonia associated with Sweet's syndrome. We present the clinical and laboratory characteristics, as well as the response to treatment, of all cases of cryptogenic organizing pneumonia reported in patients with Sweet's syndrome. CONCLUSIONS: Cryptogenic organizing pneumonia is a rare manifestation of Sweet's syndrome, which may be complicated by respiratory failure. Prompt treatment with corticosteroids usually leads to clinical and radiographic improvement.

Translocation (6;13)(p21;q14.1) as a rare nonrandom cytogenetic abnormality in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is associated with recurrent cytogenetic abnormalities that are important prognostic indicators and may influence treatment choices. Nonetheless, several chromosome abnormalities have not yet been completely determined, because of the low mitotic in vitro activity of B-CLL cells. Now, novel technologies such as stimulation of CLL cells with new B-cell mitogens have helped to overcome this problem. We present here a novel conventional and molecular cytogenetic study of a CLL patient with t(6;13)(p21;q14.1), a rare chromosomal aberration. The findings contribute to the identification of rare recurrent aberrations and of any prognostic effect in CLL that could be used for prognostic and therapeutic purposes. The present study demonstrates that t(6;13)(p21;q14.1) as a secondary event to the interstitial deletion in 13q14 region, resulting in the loss of RB1, is a rare but nonrandom abnormality in CLL, resistant to the current treatment CLL protocols with a rather favorable or intermediate prognosis but definitely not an adverse prognosis. Further studies in more CLL patients are required to delineate the prognostic value of t(6;13)(p21;q14.1) and to identify any candidate genes with potential role in the pathogenesis of the disease.

Jumping translocations in hematological malignancies: a cytogenetic study of five cases.

Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now.