-

-

-

Anemia

68 yrs

F

-

+ acute splenomegaly

-

-

9.13; RBC: 2.37

6.7

11

5

AML with a translocation or inversion in chromosome 3; Refractory acute myelogenous leukemia with poor risk cytogenetics, pancytopenia secondary to refractory AML, acute Splenomegaly, fatigue, petechiae, dyspnea on exertion, neutropenic fever, refractory thrombocytopenia with hematuria and persistence of disease.

CD34: positive in blasts that account for 45% of cellularity; CD61: positive in megakaryocytes. MPO: Positive in background myeloid cells. Negative in blasts. E-Cadherin and glycophorin: Highlights markedly decreased erythroid precursors

Not performed

The marrow cellularity is approximately 90% (biopsy/clot); Erythroid elements: Markedly decreased number. Normoblastic; Myeloid elements: Left shifted with increased blasts. Blasts account for 18% of cells in the dilute aspirate and about 45 of cells in the CD34 immunostained biopsy. Eosinophilia is seen on biopsy specimen; Megakaryocytes: Markedly increased in number with clustering and markedly dyspoietic morphology (small hypolobulated, dysjointed nuclei, hyperlobed); Reticulin stain shows Grade 1 fibrosis.

Not performed

Acute myelogenous leukemia

02-2017

Reduced dose of anthracycline therapy due to cardiac function; Cytarabine and idarubicin; Dacogen; Nivolumab; Decitabine; Hydroxyurea

-

-

-

A

05-2017

3

Bone marrow

24 and 48 hours unstimulated cultures

GTG banding

45,XX,t(3;3)(p24;q26),-7[20]

Fluorescence in situ Hybridization (FISH)

Confirmatory FISH using the Cytocell EVI1 Breakapart Probe (REF: LPH 036-A / LPH 036-A50) was performed on cells harvested from 24 hour bone marrow culture. The FISH probe mixture consists of a 156 kb probe telomeric to the D3S4415 marker including the LRRC34 gene (red, R), a 179 kb probe including the entire EVI1 (MECOM) gene plus flanking regions (green, G), and a 559 kb probe centromeric to the EVI1 gene including the D3S3364 marker (aqua, A), all within the 3q26.2 region. Interphase cells showed a 1R/1GA/1RGA signal pattern, corresponding to one split red/green signal with the aqua signal remaining with the green signal, confirming the translocation breakpoint between the EVI1 and LRRC34 genes (Figure 2). However, the partner of EVI1 resulting from the translocation remains unknown.

Rearrangements involving the 3q26 region have been described in up to 10% of acute myeloid leukemias (AML), chronic myeloid leukemias in blast crisis (CML BC), and myelodysplastic syndrome (Poppe 2006). The most common rearrangement is a paracentric inversion of the long arm, inv(3)(q21q26), although multiple rearrangements of this region have been described (Huret 2005, Jancuskova 2014, Lawce 2017). While the breakpoints are variable and may include translocations, inversions or other structural complexities, they unanimously result in EVI1 overexpression. Interphase FISH assays have been used to detect rearrangements involving the EVI1 locus at 3q26 (Wieser 2003). Monosomy 7 is also frequently present, and is associated with a poorer prognosis (Haferlach 2012, Huret 2005, Lugthart 2010). While multiple partners have been identified for EVI1, the partner of EVI1 in rearrangements involving 3p24 and 3q26 is unknown. Similar to the current case, a pericentric inversion involving both the short and long arms of chromosome 3, inv(3)(p24q26), has been reported in ten cases (Haferlach 2012), with elevated EVI1 expression reported. Therefore, identification of the partner gene warrants further investigation.