Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus

Abstract

3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity. From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated. The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy. This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.