title: A pericentric inv(9)(p22q34) of the der(9)t(9;22)(q34;q11.2) is a recurrent secondary anomaly in Ph-positive leukemia.
abstract: A pericentric inv(9)(p22q34) of the derivative chromosome 9 that resulted from a standard t(9;22)(q34;q11.2) was identified by R-banding karyotypic analysis and fluorescence in situ hybridization (FISH) assays in 4 (0.18%) of 2,200 Philadelphia chromosome (Ph)-positive leukemia patients, including 3 with chronic myeloid leukemia (CML) in chronic phase and 1 with acute myeloid leukemia (AML) in our hospital since 2004. All four patients had two malignant clones: one with only t(9;22)(q34;q11.2) and another with der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) that resulted in the separation of the ABL1/BCR fusion gene. No metaphases with only inv(9)(p22q34) were seen in any of them. FISH also found a deletion of partial sequence of BCR on der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) in 67.5% of bone marrow cells in the AML patient, but did not detect the deletion of the sequence of ASS/9q34 in these four patients. Reverse transcriptase-polymerase chain reaction revealed a b3a2 type of BCR/ABL1 fusion transcript in all of them, proving their disease to be Ph-positive leukemia. On reviewing the literature, only two solitary Ph-positive leukemia patients have been noticed to have the inv(9)(p22q34) anomaly. These two patients, together with our four documented patients, indicate that inv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Despite receiving hydroxyurea therapy (n = 3 patients), combined chemotherapy (n = 2), even imatinib treatment (n = 1), three patients, including one with AML and two with CML (one of whom progressed into the lymphoblastic blast phase), died with survival times of 28 days, 13 months, and 34 months, respectively. Only one patient with CML remained alive for 5.5 months. Their negative outcome implies that inv(9)(p22q34) has an unfavorable impact on prognosis. Presently, no firm conclusions can be drawn from this study. Because the case number reported here is very small, more patients with this anomaly need to be investigated to elucidate its true prognostic significance.
authors.affiliation: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, 188 Shizi Street, Suzhou 215006, PR China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Pan
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Xue
authors.forename: Huiying
authors.initials: H
authors.lastname: Qiu
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yafang
authors.initials: Y
authors.lastname: Wu
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction