Myeloproliferative neoplasm with ETV6-ABL1 fusion: a case report and literature review.

ETV6-ABL1 is a rare gene fusion with oncogenic properties, reported so far in 28 patients presenting a variety of haematological malignancies associated with clinical outcome, including chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and chronic myeloproliferative neoplasm (cMPN). Here we report on a 46-year-old female who presented with Philadelphia negative CML, positive for the ETV6-ABL1 fusion. Whole genome screening carried out with oligonucleotide arrays showed a subtle loss at 12p13 and cryptic imbalances within the 9q34.3 region in a highly unstable genome. FISH mapping with custom BAC probes identified two breakpoints 5 Mb apart within the 9q34 region, together with a break at 12p13. While FISH with commercial BCR-ABL1 probes failed to detect any ABL1 changes, the ETV6 break-apart probe conclusively identified the ETV6-ABL1 fusion thus determining the probe's role as the primary diagnostic FISH test for this chimeric oncogene. In addition, we confirm the association of the ETV6-ABL1 fusion with imatinib resistance reported so far in three other patients, while recording excellent response to the 2nd generation tyrosine kinase inhibitor (TKI) nilotinib. In summary, we highlight the value of ETV6 FISH as a diagnostic test and the therapy resistance of ETV6-ABL1 positive disorders to imatinib.

The cranial rhythmic impulse and excessive crying of infancy.

BACKGROUND: Osteopathic physicians believe that the birthing process causes cranial dysfunction that may be manifested in somatic symptoms, one of which is excessive crying of infancy. Cranial dysfunction can be determined by assessing the cranial rhythmic impulse (CRI). OBJECTIVE: The objective of this study is to examine whether an abnormal CRI is associated with excessive crying of infancy. DESIGN: Full-term infants in the well-baby nursery of an urban public hospital in the Bronx, New York were enrolled. Two (2) osteopathic physicians independently measured the CRI in infants before discharge. One (1) osteopath repeated the CRI measurement at 2 weeks. At 6 weeks, an investigator blinded to the CRI and birth data assessed infant crying using the modified Ames Cry Score via telephone interview with the primary caretaker. The caretaker was also asked about maternal stress, use of home or cultural remedies, and the infant's diet. The main outcome measure was the presence of excessive crying. RESULTS: One hundred and thirty-nine (139) patients were included in the final sample. The overall incidence of excessive crying was 41.7%. Excessive crying was associated with an abnormal CRI at 2 weeks (p < 0.001) but not with the CRI at birth (p = 0.23). Infants with an abnormal CRI at 2 weeks were 6.8 times (95% confidence intervals 2.2, 20.6) more likely to develop excessive crying than infants with a normal CRI. Infant diet was independently associated with excessive crying. Inter-rater agreement for CRI measurement was 0.70 using the kappa statistic. CONCLUSIONS: These data suggest that an abnormal CRI at 2 weeks of age may be associated with excessive crying.

Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression.

BACKGROUND AND OBJECTIVES: The acquisition of additional cytogenetic changes (clonal evolution, CE) during treatment of chronic myeloid leukemia (CML) with imatinib mesylate is currently regarded as an index of increasing resistance to imatinib. Therefore, to investigate whether CE as an isolated event increases the risk of disease progression during imatinib treatment, we compared the outcome of patients with CML in chronic phase (CML-CP) who developed CE whilst in complete hematologic remission with the outcome of comparable patients in complete hematologic remission who showed no evidence of CE. DESIGN AND METHODS: We serially studied cytogenetic findings in 102 patients receiving the Abl-tyrosine kinase inhibitor, imatinib mesylate, as sole agent to treat CML-CP who had no evidence of CE before initiation of imatinib treatment. RESULTS: CE was identified during treatment with imatinib in 15 patients, 10 of whom were in complete hematologic remission. In most cases these changes occurred exclusively in the Ph+ population but in three patients additional changes occurred in a co-existing Ph-negative population. Patients with de novo CE in the absence of any other sign of disease progression had a significantly higher incidence of progression by 18 months than did non-CE patients (progression-free survival 34.3% (CI 10.5-69.8%) vs. 94.1% (CI 80.6-98.4%), p<0.0001). INTERPRETATION AND CONCLUSIONS: Based on this relatively small series of patients, we conclude that acquisition of clonal evolution increases the risk of subsequent disease progression also in CML patients in complete hematologic remission on imatinib.