Experts Discuss Latest In Hematology Research At Suntec Singapore

Hematology experts gathered at Suntec Singapore from March 29-30, 2014 to discuss the latest in blood disorders research.

Asian Scientist (Apr. 7, 2014) – Hematologists from around the world gathered in Singapore to discuss the latest breakthroughs in blood disorders research at the American Society of Hematology’s (ASH) Highlights of ASH® in Asia meeting, held from March 29-30 at the Suntec Singapore Convention & Exhibition Center.

The conference was co-organized by ASH, the world’s largest professional society concerned with the causes and treatments of blood disorders, and the Cancer Science Institute of the National University of Singapore (CSI, NUS).

A meeting of hematology experts

During the two-day conference, the only official Highlights of ASH® meeting in Asia, 13 expert speakers discussed the most significant research abstracts and topics presented at the ASH Annual Meeting, which was held from December 7-10, 2013 in New Orleans, USA.

The speakers took part in six panel discussions moderated by leading hematology experts from around Asia, fielding questions from delegates at the conference. The delegates also viewed 26 posters that were presented at the 2013 ASH Annual Meeting by researchers from Asia and Australia.

Topics covered included latest discoveries in the causes and treatment of blood cancers (including various types of leukemia, lymphoma and myeloma) and other blood disorders (including hemophilia, thrombosis and thrombocytopenia).

Genomics in hematology

One of the hottest topics in hematology is the use of genomic and genetic analyses to unravel the causes of various blood disorders and to improve treatment of these disorders. Asian Scientist Magazine attended a talk titled “Genomics in Hematology 101” by Dr Charles Mullighan, an expert on the genetic basis of leukemia, who gave an overview of the various high-throughput sequencing technologies that are increasingly being used in the study of hematologic disorders.

Dr Mullighan was optimistic that these so-called “next-generation sequencing” technologies would lead to better treatment for patients but cautioned that many challenges must be overcome before these technologies can be routinely used in the clinic.

“Sequencing is increasingly standardized and straightforward, but data analysis and clinical implementation are complex,” he said.

Dr Charles Mullighan speaking at Highlights of ASH in Asia 2014.
Dr Charles Mullighan speaking at Highlights of ASH in Asia 2014.

Dr Mullighan went on to highlight eight scientific abstracts presented at ASH that reported using genomic analyses to gain insights into the biology of blood disorders, as well as suggest new diagnostic tests and therapeutic approaches for blood malignancies.

One of the studies, carried out by Dr Mullighan’s group at St Jude Children’s Research Hospital in the United States, used next-generation sequencing to identify potential drug targets for treating Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL), a high-risk childhood ALL subtype that was recently identified through genomic analysis.

Ph-like ALL accounts for as much as 15 percent of childhood ALL and is associated with a high risk of relapse and poor outcome. Ph-like ALL is named after a chromosomal rearrangement known as the Philadelphia chromosome, which is associated with another ALL subtype known as Philadelphia-positive ALL (Ph+ ALL). The Ph+ and Ph-like subtypes share similar gene expression profiles, but patients with Ph-like ALL lack the fusion of the BCR and ABL1 genes that is a hallmark of Ph+ ALL.

Investigators led by Dr Mullighan had previously identified two subgroups in a pilot study of 15 patients with Ph-like ALL: about half harbored CRLF2 gene rearrangements while the other half exhibited a variety of kinase alterations. They further showed that some of these genetic alterations activate cancer-promoting processes that can be targeted using existing drugs.

In the latest study, the research group expanded their study to include over 1,000 patients with B-progenitor ALL (B-ALL). Through their analysis, they confirmed that about half of Ph-like B-ALL cases in all age-groups harbored rearrangements of the CRLF2 gene.

Their new study also found that the frequency of Ph-like ALL increases with age: less than 14 percent of childhood B-ALL cases (less than 16 years old) belong to the Ph-like ALL subtype while more than 21 percent of adolescent (16-21 years old) B-ALL cases are Ph-like. The percentage of Ph-like ALL cases further rises to more than 26 percent in young adult (21-29 years old) B-ALL cases.

According to Dr Mullighan, these results show that Ph-like ALL is a common subtype of high-risk B-ALL. Furthermore, the study highlighted a lack of knowledge about the genetic alterations that drive Ph-like ALL in the absence of CRLF2 gene rearrangements.

Therefore, Dr Mullighan’s group used high-throughput sequencing methods to characterize the full range of genetic alterations that affect kinase genes in the Ph-like B-ALL cases where CRLF2 gene rearrangements were not detected. They focused on genes that code for kinases because these are important drug targets that function by adding phosphate groups to other proteins, a crucial modification that can change the protein’s function and activity.

Through this analysis, Dr Mullighan’s team identified kinase activating mutations in more than 90 percent of the cases sequenced and found that the majority of these may respond to ABL/JAK class inhibitors which are already being used to treat B-ALL patients in the clinic. He noted that another ASH abstract presented by a Japanese group reported similar findings after performing a genetic analysis of Ph-like ALL in Japanese patients.

Sequencing in the clinic

Dr Mullighan presented a clinical case study to illustrate how genetic analyses are already improving treatment for patients with Ph-like ALL: A ten-year-old boy with refractory B-ALL who was found to be positive for a EBF1-PDGFRB gene fusion showed morphologic remission and immediate clinical improvement after one week of imatinib treatment. He remains in remission at one year.

Despite this success story, few genomic findings have been adopted into clinical practice because of various limitations. Dr Mullighan ended his talk by highlighting an effort started at Memorial Sloan Kettering Cancer Center to implement next-generation sequencing in the clinic for assessing the genomic landscape of hematologic malignancies.

He pointed out the key features of the effort which may help accelerate the path towards whole genome sequencing at diagnosis: a robust platform, a combination of approaches to cover a wide spectrum of alterations, and the generation of a report that is clinically relevant. In particular, the sequencing report indicates if the patient is eligible for currently approved therapies and on-going genotype-directed clinical trials.

Asian Scientist Magazine is a media partner of Suntec Singapore Convention & Exhibition Center.


Copyright: Asian Scientist Magazine; Photo: CSI, NUS.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Yew Chung is a postdoctoral research fellow at the Duke-NUS Graduate Medical School, Singapore.

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