PMC6862801_01
a Peripheral blood shows marked leukocytosis with numerous blasts and promyelocytes, dyspoietic granulocytes with nuclear hypolobation and hypogranularity, and dyspoietic erythroid precursors. b Bone marrow core biopsy is hypercellular for age (80%). Maturing granulopoiesis and erythropoiesis are replaced by sheets of immature cells. Megakaryocytes are decreased and have atypical morphology. c Bone marrow aspirate consists of blasts which are intermediate in size with fine chromatin, prominent nucleoli and scant basophilic cytoplasm. A few dyspoietic maturing granulocytes and atypical megakaryocytes are present. d Partial karyograms of a 46,XY,+ 1,der(1;21)(p10 or q10;q10) karyotype, a 46,XY,+ 1,del(1)(p12) karyotype, and 46,XY,+ 1,der(1;14)(p10 or q10;q10),i(18)(q10) karyotype. e Whole-genome SNP microarray shows mosaic gain of chromosome 1 from 1p11 to 1qter regions and mosaic gain of chromosome 18q. f Fusion sites of recipient chromosomes of 149 jumping translocations of 1q in 48 myeloid neoplasm patients (including our patient). g A possible multi-stage process for the development and formation of 1q JTs in our patient.
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PMC6862801_01_13039_2019_460_Fig1_HTML.jpg
Fig1
Three years after diagnosis, his white blood cell count increased rapidly to 36.9 K/mcL with 20% blasts (Fig. 1a). Bone marrow biopsy (Fig. 1b) and aspirate (Fig. 1c) were hypercellular (80%) with increased reticulin fibrosis (Grade 2-3/3) and with 53% myeloblasts by aspirate differential, diagnostic of AML with myelodysplasia-related changes. Karyotype was abnormal, with unbalanced 1q JTs: 46,XY,+ 1,der(1;21)(p10 or q10;q10) [7]/46,XY,+ 1, der(1;14)(p10 or q10;q10),i(18)(q10) [5]/46,XY,+ 1,del(1)(p12, 1]/46,XY [8] (Fig. 1d). Whole-genome single nucleotide polymorphism (SNP) microarray showed mosaic gain of chromosomes 1p11-1q44 and 18q11.1-18q23, arr [hg19] 1p11q44(120,365,518_ 249,224,684)x 2-3,18q11.1q23(18, 811,960_78,014,123)x 2-3 (Fig. 1e). The 1q JTs were demonstrated to have a chromosome 1 centromere using a centromere 1 Satellite II/III FISH probe (Abbott/Vysis, Inc.), and to contain ribosomal ribonucleic acid (rRNA) genes located in nucleolar organizer regions (NORs) of short arms of the acrocentric chromosomes using an acro-p-arm probe (Abbott/Vysis, Inc.) (Fig. 1g, insertions 1-2). Telomere FISH did not show telomere repeats in fusion sites of the 1q JTs using telomere-specific (TTAGGG)3 probes (Applied Biosystems, Foster City, CA) (Fig. 1g, insertion 2). In terms of recipient chromosomes, among 149 1q JTs in 48 patients with myeloid neoplasms, 43% of the fusions occurred in short arms of acrocentric chromosomes, 38% occurred in telomeric regions of chromosome arms, 11% occurred in the pericentromeric/centromere regions, and 8% occurred in interstitial regions of recipient chromosomes (Fig. 1f).