Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2(V617F) and response to erythropoietin therapy.
BACKGROUND
Patients who have myelofibrosis with myeloid metaplasia (MMM) display recurrent, albeit nonspecific cytogenetic abnormalities that are diverse prognostically. For the current study, the authors explored the relation between specific cytogenetic clones and JAK2(V617F) mutational status in patients with MMM and the effects on treatment response to erythropoietin (Epo).


METHODS
Concomitantly collected blood granulocytes and bone marrow were processed for JAK2(V617F) mutation analysis and cytogenetic studies, respectively. Genomic DNA was amplified by polymerase chain reaction, and fluorescent dye chemistry sequencing was performed by using the same primers that were used for amplification.


RESULTS
Among 105 study patients, cytogenetic abnormalities were detected in 47 patients (45%), and the JAK2(V617F) mutation was detected in 52 patients (50%). Comparison of mutational frequencies between favorable (normal, sole 13q-, or 20q- clones; n = 70 patients) and unfavorable (all other abnormalities; n = 35 patients) cytogenetic categories revealed a significantly different incidence of homozygous JAK2(V617F) between them (9% vs. 23%, respectively; P = .04). Furthermore, the mutant allele coexisted with several recurrent cytogenetic lesions. Among 25 patients who received Epo either alone (n = 17 patients) or in combination with hydroxyurea (n = 8 patients), 4 patients (16%) achieved a response, and none of them were homozygous for JAK2(V617F). Conversely, a response was more likely (P = .0001) in the presence of favorable cytogenetic abnormalities (i.e., 3 of 4 responders carried sole 13q- or 20q- clones).


CONCLUSIONS
Unfavorable and favorable cytogenetic clones in MMM clustered with homozygosity for JAK2(V617F) and treatment response to Epo-based therapy, respectively.
Tefferi
Ayalew
A
Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA. tefferi.ayalew@mayo.edu
Strand
Jacob J
JJ
Lasho
Terra L
TL
Elliott
Michelle A
MA
Li
Chin-Yang
CY
Mesa
Ruben A
RA
Dewald
Gordon W
GW
D002999:Clone Cells; D004252:DNA Mutational Analysis; D004921:Erythropoietin / Q000627:therapeutic use*; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2; D009154:Mutation; D055728:Primary Myelofibrosis / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D016896:Treatment Outcome
D011518:Proto-Oncogene Proteins; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2